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Rose, Jed Eugene

Overview:

We are pursuing three main lines of research:

1) Brain imaging of the effects of nicotine and cigarette smoking: We have used Positron Emission Tomography (PET) methods to analyze regional cerebral blood flow responses to nicotine, administered either intravenously or inhaled in cigarettes. Our aim is to identify brain substrates mediating the addictive properties of nicotine. Preliminary results have shown alterations in the pattern of regional cerebral blood flow, involving frontal cortex, amygdala and other brain regions. We will continue to delineate the similarities and differences between the effects of nicotine and other drugs on regional brain activity, and plan to monitor the changes in response to nicotine after smoking cessation with nicotine antagonist treatment.

2) Analysis of airway sensory components of smoking reinforcement: We have continued the study the role of sensorimotor aspects of cigarette smoking in relieving craving for cigarettes and regulating smoke intake. We completed a study of the effects of intravenous nicotine presented alone or in combination with the sensorimotor aspects of smoking using de-nicotinized cigarette smoke. Craving for cigarettes was relieved more effectively by the de-nicotinized smoke than by the intravenous nicotine. Current studies underway at the Clinical Research Unit will further investigate the subjective effects of i.v. nicotine and de-nicotinized cigarette smoke, using a wider range of nicotine doses. Possible predictors of clinical outcome following nicotine skin patch treatment will be identified based on acute responses to the pharmacologic effects of nicotine in the laboratory.

We are also continuing to further the clinical application of these findings by developing substitutes that provide the airways sensory effects of smoking (e.g. citric acid aerosol).


3) Agonist/antagonist combination treatment for drug dependence: In a double blind smoking cessation trial using mecamylamine, a nicotinic antagonist, in combination with nicotine skin patches, we found that addition of the antagonist substantially increases smoking abstinence throughout the 1 year follow-up. Two additional studies that we conducted support the view that pre-treatment with mecamylamine prior to smoking cessation may be a critical factor in achieving high success rates. By blocking reinforcing effects of nicotine, smoking behavior may be partially extinguished, thereby facilitating subsequent smoking cessation. We recently completed a Phase II FDA trial evaluating a transdermal patch delivering nicotine and mecamylamine, which replicated our previous results. It is anticipated that an NDA pertaining to the new skin patch will be submitted in 1997. Continuing studies in our program will determine the optimal dose and duration of treatment. We also have initiated studies to extend this approach to the treatment of other drug dependencies, including cocaine.

Positions:

Professor in Psychiatry and Behavioral Sciences

Psychiatry & Behavioral Sciences, Addictions
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1978

Ph.D. — University of California at San Diego

News:

Grants:

E-cigarettes: deposition, absorption and brain accumulation of nicotine

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 01, 2017
End Date
July 31, 2022

Center for Adaptive Treatment of Cigarette Addiction

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 15, 2010
End Date
May 31, 2020

The Role of Nicotine and Non-Nicotine Alkaloids in E-Cigarette Use and Dependence

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
February 15, 2015
End Date
November 30, 2018

Alpha 5 Nicotinic Receptor Subunit Gene Polymorphisms and Smoking Addiction

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
March 15, 2013
End Date
February 28, 2018

Novel Approach to Quantify Nicotinic Receptor Upregulation in Smokers

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 01, 2014
End Date
August 31, 2017

P50 Supplement

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 15, 2010
End Date
June 30, 2015

Brain Substrates of Extinction-Based Treatment for Nicotine Dependence

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 15, 2008
End Date
June 30, 2014

Optimal Smoking Cessation Treatment in PTSD

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
July 25, 2003
End Date
April 30, 2014

Effects of Cigarette Mentholation on Brain Nicotine Accumulation During Smoking

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
August 01, 2011
End Date
July 31, 2013

Neurobiology of Nicotine and Non-nicotine Components of Tobacco Addiction

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
May 15, 2008
End Date
March 31, 2013

Improving the efficacy of anti-nicotine immunotherapy

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 30, 2009
End Date
August 31, 2012

Smoking & Anxiety In Posttraumatic Stress Disorder

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 30, 1998
End Date
February 29, 2012

Stress and Behavior in Health and Disease

Administered By
Psychiatry & Behavioral Sciences, Behavioral Medicine
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 1989
End Date
June 30, 2011

Neuroimaging Attentional Impairment During Abstinence

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 2004
End Date
June 30, 2009

The Effect of Smoking on Startle & PPI in PTSD

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
April 01, 2006
End Date
January 31, 2009

Oral nicotine replacement for Smoking Cessation

Administered By
Medicine, General Internal Medicine
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
September 30, 2003
End Date
July 31, 2006

Drug Cue Reactivity in Smokers: An fMRI Investigation

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 30, 2002
End Date
September 29, 2004

Scaling The Reinforcing Value Of Cigarette Smoke

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
February 11, 1999
End Date
January 31, 2004

Nicotinic Influences on Alcohol Use and Dependence

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 29, 1996
End Date
August 31, 2002

Dopaminergic Mechanisms Of Nicotine Addiction

Administered By
Psychiatry & Behavioral Sciences, General Psychiatry
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 15, 1997
End Date
June 30, 2002

Nicotine Tolerance and Blockade in Cigarette Smokers

Administered By
Psychiatry & Behavioral Sciences, Addictions
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 1996
End Date
July 31, 2000

Nicotinic Influences On Alcohol Use And Dependence

Administered By
Psychiatry & Behavioral Sciences, Translational Neuroscience
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 29, 1996
End Date
August 31, 1999

Nicotine Tolerance And Blockade In Cigarette Smokers

Administered By
Psychiatry & Behavioral Sciences, Translational Neuroscience
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 1996
End Date
July 31, 1999

Scaling The Reinforcing Value Of Cigarette Smoke

Administered By
Psychiatry & Behavioral Sciences, Translational Neuroscience
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1993
End Date
July 31, 1999

Dopaminergic Mechanisms In Nicotine Addiction

Administered By
Psychiatry & Behavioral Sciences, Translational Neuroscience
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 15, 1997
End Date
June 30, 1999

Phentermine And Fenfluramine For Smoking Cestation

Administered By
Psychiatry & Behavioral Sciences, Translational Neuroscience
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
February 01, 1997
End Date
January 31, 1999

Neuroanatomical Substrates Of Nicotine Addiction

Administered By
Psychiatry & Behavioral Sciences, Translational Neuroscience
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 1995
End Date
August 31, 1998

Caffine Effects On Stress Reactivy

Administered By
Psychiatry & Behavioral Sciences, Behavioral Medicine
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
May 01, 1995
End Date
March 31, 1998

Drive To Smoke And Dopamine Blockade

Administered By
Psychiatry & Behavioral Sciences, Translational Neuroscience
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
July 01, 1994
End Date
November 30, 1997

Neuroanatomiacal Substrates Of Nicotine Addiction

Administered By
Psychiatry & Behavioral Sciences, Translational Neuroscience
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 1995
End Date
August 31, 1997

Biobehavioral Factors In Coronary Heart Disease

Administered By
Psychiatry & Behavioral Sciences, Behavioral Medicine
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
May 01, 1994
End Date
April 30, 1996

Biobehaviorial Factors In Coronary Heart Disease

Administered By
Psychiatry & Behavioral Sciences, Behavioral Medicine
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
May 01, 1993
End Date
April 30, 1996

Caffine'S Effects On Smoking And Nicotine Withdrawal

Administered By
Psychiatry & Behavioral Sciences, Behavioral Medicine
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
July 01, 1993
End Date
June 30, 1995

Scaling The Reinforcing Value Of Cigarette Smoke

Administered By
Psychiatry & Behavioral Sciences, Translational Neuroscience
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 1993
End Date
August 31, 1994
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Publications:

The effects of nicotine and non-nicotine smoking factors on working memory and associated brain function.

Smoking abstinence impairs executive function, which may promote continued smoking behavior and relapse. The differential influence of nicotine and non-nicotine (i.e. sensory, motor) smoking factors and related neural substrates is not known. In a fully factorial, within-subjects design, 33 smokers underwent fMRI scanning following 24 hours of wearing a nicotine or placebo patch while smoking very low nicotine content cigarettes or remaining abstinent from smoking. During scanning, blood oxygenation level-dependent (BOLD) signal was acquired while participants performed a verbal N-back task. Following 24-hour placebo (versus nicotine) administration, accuracy on the N-back task was significantly worse and task-related BOLD signal lower in dorsomedial frontal cortex. These effects were observed irrespective of smoking. Our data provide novel evidence that abstinence-induced deficits in working memory and changes in underlying brain function are due in large part to abstinence from nicotine compared with non-nicotine factors. This work has implications both for designing interventions that target abstinence-induced cognitive deficits and for nicotine-reduction policy.

Authors
McClernon, FJ; Froeliger, B; Rose, JE; Kozink, RV; Addicott, MA; Sweitzer, MM; Westman, EC; Van Wert, DM
MLA Citation
McClernon, FJ, Froeliger, B, Rose, JE, Kozink, RV, Addicott, MA, Sweitzer, MM, Westman, EC, and Van Wert, DM. "The effects of nicotine and non-nicotine smoking factors on working memory and associated brain function." Addiction biology 21.4 (July 2016): 954-961.
PMID
25904425
Source
epmc
Published In
Addiction Biology
Volume
21
Issue
4
Publish Date
2016
Start Page
954
End Page
961
DOI
10.1111/adb.12253

Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.

Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2C agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with the lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, an acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (p<0.05) or 13.3-mg/kg of pyrilamine alone (p<0.0005). In the lorcaserin-dextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self-administration replicating previous findings. Augmenting interactions were observed with dextromethorphan and pyrilamine as well as lorcaserin. These findings suggest that combination therapy may be more effective smoking cessation treatments than monotherapy.

Authors
Briggs, SA; Hall, BJ; Wells, C; Slade, S; Jaskowski, P; Morrison, M; Rezvani, AH; Rose, JE; Levin, ED
MLA Citation
Briggs, SA, Hall, BJ, Wells, C, Slade, S, Jaskowski, P, Morrison, M, Rezvani, AH, Rose, JE, and Levin, ED. "Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats." Pharmacology, biochemistry, and behavior 142 (March 2016): 1-7.
PMID
26704812
Source
epmc
Published In
Pharmacology Biochemistry and Behavior
Volume
142
Publish Date
2016
Start Page
1
End Page
7
DOI
10.1016/j.pbb.2015.12.004

Increased Functional Connectivity in an Insula-Based Network is Associated with Improved Smoking Cessation Outcomes.

Little is known regarding the underlying neurobiology of smoking cessation. Neuroimaging studies indicate a role for the insula in connecting the interoceptive awareness of tobacco craving with a larger brain network that motivates smoking. We investigated differences in insula-based functional connectivity between smokers who did not relapse during a quit attempt vs those who relapsed. Smokers (n=85) underwent a resting-state functional connectivity scan and were then randomized into two groups (either smoking usual brand cigarettes or smoking very low nicotine cigarettes plus nicotine replacement therapy) for 30 days before their target quit date. Following the quit date, all participants received nicotine replacement therapy and their smoking behavior was observed for 10 weeks. Participants were subsequently classified as nonrelapsed (n=44) or relapsed (i.e., seven consecutive days of smoking ⩾1 cigarette/day; n=41). The right and left insula, as well as insula subdivisions (posterior, ventroanterior, and dorsoanterior) were used as seed regions of interest in the connectivity analysis. Using the right and left whole-insula seed regions, the nonrelapsed group had greater functional connectivity than the relapsed group with the bilateral pre- and postcentral gyri. This effect was isolated to the right and left posterior insula seed regions. Our results suggest that relapse vulnerability is associated with weaker connectivity between the posterior insula and primary sensorimotor cortices. Perhaps greater connectivity in this network improves the ability to inhibit a motor response to cigarette cravings when those cravings conflict with a goal to remain abstinent. These results are consistent with recent studies demonstrating a positive relationship between insula-related functional connectivity and cessation likelihood among neurologically intact smokers.

Authors
Addicott, MA; Sweitzer, MM; Froeliger, B; Rose, JE; McClernon, FJ
MLA Citation
Addicott, MA, Sweitzer, MM, Froeliger, B, Rose, JE, and McClernon, FJ. "Increased Functional Connectivity in an Insula-Based Network is Associated with Improved Smoking Cessation Outcomes." Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 40.11 (October 2015): 2648-2656.
PMID
25895453
Source
epmc
Published In
Neuropsychopharmacology (Nature)
Volume
40
Issue
11
Publish Date
2015
Start Page
2648
End Page
2656
DOI
10.1038/npp.2015.114

Amitifadine, a triple monoamine re-uptake inhibitor, reduces nicotine self-administration in female rats.

A wider diversity of drug treatments to aid smoking cessation is needed to help tailor the most efficacious treatment for different types of smokers. This study was conducted to determine whether amitifadine, which inhibits re-uptake of dopamine, norepinephrine and serotonin, would decrease nicotine self-administration at doses that do not cause adverse side effects. Adult female Sprague-Dawley rats were trained to self-administer nicotine intravenous (IV) and were given acute doses of amitifadine in a repeated measures counterbalanced design. Effects of amitifadine on locomotor activity and food motivated responding were also evaluated. Chronic amitifadine effects were also examined. The 30 mg/kg amitifadine dose significantly reduced nicotine self-administration. The 5 and 10 mg/kg doses reduced nicotine self-administration during the first 15 min of the session when the greatest amount of nicotine was self-administered. The 30 mg/kg amitifadine dose, but not the lower doses caused a significant reduction in locomotor activity averaged over the one-hour session and reduced food motivated responding. The 10 mg/kg dose caused hypoactivity at the beginning of the session, but 5 mg/kg did not cause any hypoactivity. The effects of chronic amitifadine treatment (10 mg/kg) over the course of 15 sessions was also determined. Amitifadine caused a significant reduction in nicotine self-administration, which was not seen to diminish over two consecutive weeks of treatment and a week after enforced abstinence. Amitifadine significantly reduced nicotine self-administration. This prompts further research to determine if amitifadine might be an effective treatment for smoking cessation.

Authors
Levin, ED; Wells, C; Johnson, JE; Rezvani, AH; Bymaster, FP; Rose, JE
MLA Citation
Levin, ED, Wells, C, Johnson, JE, Rezvani, AH, Bymaster, FP, and Rose, JE. "Amitifadine, a triple monoamine re-uptake inhibitor, reduces nicotine self-administration in female rats." European journal of pharmacology 764 (October 2015): 30-37.
PMID
26101069
Source
epmc
Published In
European Journal of Pharmacology
Volume
764
Publish Date
2015
Start Page
30
End Page
37
DOI
10.1016/j.ejphar.2015.06.041

Response to Gorelick.

Authors
Rose, JE; Behm, FM
MLA Citation
Rose, JE, and Behm, FM. "Response to Gorelick." The American journal of psychiatry 172.4 (April 2015): 395-. (Letter)
PMID
25827038
Source
epmc
Published In
American Journal of Psychiatry
Volume
172
Issue
4
Publish Date
2015
Start Page
395
DOI
10.1176/appi.ajp.2015.14111429r

Sex-specific effects of cigarette mentholation on brain nicotine accumulation and smoking behavior.

Menthol cigarettes are likely associated with greater risks of smoking dependence than non-menthol cigarettes. We sought to test the hypothesis that menthol increases the rate of brain nicotine accumulation (BNA) during smoking and thereby enhances its addictive effects. In a counter-balanced cross-over design, 10 menthol and 9 non-menthol smokers (10 females and 9 males; mean age 44.3) underwent two study phases. In each phase, the participant smoked exclusively either menthol or non-menthol research cigarettes for approximately 1 week prior to a positron emission tomography (PET) scan session, during which the subject's head was scanned following inhalation of a single puff of smoke from a cigarette containing (11)C-nicotine. No differences in initial slope, Cmax, area under curve (AUC), and T1/2 of BNA were found between menthol and non-menthol cigarettes across all subjects; however, menthol relative to non-menthol cigarettes were associated with steeper initial slopes in men (p=0.008). Unexpectedly, women had faster BNA as indicated by greater values of the initial slope, Cmax, AUC, and shorter T1/2 than men (all ps<0.04). The rates of BNA were significantly correlated with ratings of smoking motivations of getting a 'rush', getting relaxing effects and marginally with alleviation of craving. These results do not provide strong support for the putative role of menthol in enhancing BNA, although further studies should explore the apparent effect of menthol on BNA in men. Fast BNA during smoking and preference of sensory properties of menthol cigarettes may independently or jointly contribute to smoking dependence among women.

Authors
Zuo, Y; Mukhin, AG; Garg, S; Nazih, R; Behm, FM; Garg, PK; Rose, JE
MLA Citation
Zuo, Y, Mukhin, AG, Garg, S, Nazih, R, Behm, FM, Garg, PK, and Rose, JE. "Sex-specific effects of cigarette mentholation on brain nicotine accumulation and smoking behavior." Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 40.4 (March 2015): 884-892.
PMID
25267342
Source
epmc
Published In
Neuropsychopharmacology (Nature)
Volume
40
Issue
4
Publish Date
2015
Start Page
884
End Page
892
DOI
10.1038/npp.2014.263

Bupropion-varenicline interactions and nicotine self-administration behavior in rats.

Varenicline and bupropion each have been shown to significantly improve cessation of tobacco addiction in humans. They act through different mechanisms and the question about the potential added efficacy with their combined used has arisen. Preclinical animal models of nicotine addiction can help with the evaluation of this combined approach and what dose combinations of varenicline and bupropion may be useful for enhancing tobacco cessation. In this study, we investigated the interacting dose-effect functions of varenicline and bupropion in a rat model of nicotine self-administration. Young adult female Sprague-Dawley rats were allowed to self-administer nicotine in 1-h sessions under an FR1 reinforcement schedule. Varenicline (0.3, 1. 3 mg/kg) and bupropion (8.33, 25, 75 mg/kg) were administered alone or together 15 min before each session. The vehicle saline was the control. Higher doses of each drug alone reduced nicotine self-administration compared to control with reductions of 62% and 75% with 3 mg/kg varenicline and 75 mg/kg bupropion respectively. Lower dose varenicline which does not by itself reduce nicotine self-administration, significantly augmented bupropion effects. The 0.3 mg/kg varenicline dose combined with the 25 and 75 mg/kg bupropion doses caused greater reductions of nicotine self-administration than either dose of bupropion given alone. However, higher dose varenicline did not have this effect. Lower dose bupropion did not augment varenicline effects. Only the high bupropion dose significantly enhanced the varenicline effect. Likewise, combining 1 mg/kg varenicline with 75 mg/kg bupropion reduced self-administration to a greater extent than either dose alone. These results demonstrate that combination therapy with varenicline and bupropion may be more beneficial than monotherapy with either drug alone.

Authors
Hall, BJ; Slade, S; Wells, C; Rose, JE; Levin, ED
MLA Citation
Hall, BJ, Slade, S, Wells, C, Rose, JE, and Levin, ED. "Bupropion-varenicline interactions and nicotine self-administration behavior in rats." Pharmacology, biochemistry, and behavior 130 (March 2015): 84-89.
PMID
25616031
Source
epmc
Published In
Pharmacology Biochemistry and Behavior
Volume
130
Publish Date
2015
Start Page
84
End Page
89
DOI
10.1016/j.pbb.2015.01.009

NIH electronic cigarette workshop: developing a research agenda.

Electronic cigarettes (e-cigarettes) represent an emerging public health issue. These devices deliver nicotine along with other constituents, including flavorants, via an inhalable aerosol. Their uptake is rapidly increasing in both adults and youths, primarily among current smokers. Public debate is increasing on how these devices should be regulated and used, yet only limited peer-reviewed research exists. To develop a informed policy for e-cigarettes, their effects on human behavior, physiology, and health need to be understood.This paper describes proceedings from a National Institutes of Health-sponsored workshop, which was held in November 2013, to identify research needs related to the effects of e-cigarettes. Discussion topics included e-cigarette risks and abuse potential; the potential role for e-cigarettes in harm reduction and smoking cessation; unintended consequences of e-cigarette use, such as becoming a gateway to conventional cigarettes; and dual use of both e-cigarettes and conventional cigarettes.The research needs identified by the workshop participants included the following: standards to measure the contents and emissions of e-cigarettes; biomarkers of exposure; physiological effects of e-cigarettes on tissues and organ systems, including pulmonary and cardiovascular; information on e-cigarette users, how the devices are used, and identification of the best tools to assess these measures; factors that drive use and influence patterns of use; and appropriate methods for evaluating a potential role for e-cigarettes in smoking or nicotine cessation. To understand fully the challenges and the opportunities that e-cigarettes represent, expertise will be needed in basic, behavioral, translational, and clinical sciences.

Authors
Walton, KM; Abrams, DB; Bailey, WC; Clark, D; Connolly, GN; Djordjevic, MV; Eissenberg, TE; Fiore, MC; Goniewicz, ML; Haverkos, L; Hecht, SS; Henningfield, JE; Hughes, JR; Oncken, CA; Postow, L; Rose, JE; Wanke, KL; Yang, L; Hatsukami, DK
MLA Citation
Walton, KM, Abrams, DB, Bailey, WC, Clark, D, Connolly, GN, Djordjevic, MV, Eissenberg, TE, Fiore, MC, Goniewicz, ML, Haverkos, L, Hecht, SS, Henningfield, JE, Hughes, JR, Oncken, CA, Postow, L, Rose, JE, Wanke, KL, Yang, L, and Hatsukami, DK. "NIH electronic cigarette workshop: developing a research agenda." Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 17.2 (February 2015): 259-269.
PMID
25335949
Source
epmc
Published In
Nicotine and Tobacco Research (OUP)
Volume
17
Issue
2
Publish Date
2015
Start Page
259
End Page
269
DOI
10.1093/ntr/ntu214

Neuroanatomical circuitry mediating the sensory impact of nicotine in the central nervous system.

Direct actions of nicotine in the CNS appear to be essential for its reinforcing properties. However, activation of nicotinic acetylcholine receptors (nAChRs) on afferent sensory nerve fibers is an important component of addiction to, and withdrawal from, cigarette smoking. The aim of the present study was to identify the neuroanatomical substrates activated by the peripheral actions of nicotine and to determine whether these sites overlap brain structures stimulated by direct actions of nicotine. Mouse brains were examined by immunohistochemistry for c-Fos protein after intraperitoneal injection of either nicotine hydrogen tartrate salt (NIC; 30 and 40 μg/kg) or nicotine pyrrolidine methiodide (NIC-PM; 20 and 30 μg/kg). NIC-PM induced c-Fos immunoreactivity (IR) at multiple brain sites. In the brainstem, c-Fos IR was detected in the locus coeruleus, laterodorsal tegmental nucleus, and pedunculotegmental nucleus. In the midbrain, c-Fos IR was observed in areas overlapping the ventral tegmental area (VTA), which includes the paranigral nucleus, parainterfascicular nucleus, parabrachial pigmental area, and rostral VTA. Other structures of the nicotine brain-reward circuitry activated by NIC-PM included the hypothalamus, paraventricular thalamic nucleus, lateral habenular nucleus, hippocampus, amygdala, accumbens nucleus, piriform cortex, angular insular cortex, anterior olfactory nucleus, lateral septal nucleus, bed nucleus of stria terminalis, cingulate and medial prefrontal cortex, olfactory tubercle, and medial and lateral orbital cortex. NIC, acting through central and peripheral nAChRs, produced c-Fos IR in areas that overlapped NIC-PM-induced c-Fos-expressing sites. These neuroanatomical data are the first to demonstrate that the CNS structures that are the direct targets of nicotine are also anatomical substrates for the peripheral sensory impact of nicotine.

Authors
Dehkordi, O; Rose, JE; Asadi, S; Manaye, KF; Millis, RM; Jayam-Trouth, A
MLA Citation
Dehkordi, O, Rose, JE, Asadi, S, Manaye, KF, Millis, RM, and Jayam-Trouth, A. "Neuroanatomical circuitry mediating the sensory impact of nicotine in the central nervous system." Journal of neuroscience research 93.2 (February 2015): 230-243.
PMID
25223294
Source
epmc
Published In
Journal of Neuroscience Research
Volume
93
Issue
2
Publish Date
2015
Start Page
230
End Page
243
DOI
10.1002/jnr.23477

Sex-specific effects of cigarette mentholation on brain nicotine accumulation and smoking behavior

© 2015 American College of Neuropsychopharmacology. All rights reserved. Menthol cigarettes are likely associated with greater risks of smoking dependence than non-menthol cigarettes. We sought to test the hypothesis that menthol increases the rate of brain nicotine accumulation (BNA) during smoking and thereby enhances its addictive effects. In a counter-balanced cross-over design, 10 menthol and 9 non-menthol smokers (10 females and 9 males; mean age 44.3) underwent two study phases. In each phase, the participant smoked exclusively either menthol or non-menthol research cigarettes for approximately 1 week prior to a positron emission tomography (PET) scan session, during which the subject's head was scanned following inhalation of a single puff of smoke from a cigarette containing < sup > 11 < /sup > C-nicotine. No differences in initial slope, C < inf > max < /inf > , area under curve (AUC), and T < inf > 1/2 < /inf > of BNA were found between menthol and non-menthol cigarettes across all subjects; however, menthol relative to non-menthol cigarettes were associated with steeper initial slopes in men (p=0.008). Unexpectedly, women had faster BNA as indicated by greater values of the initial slope, C < inf > max < /inf > , AUC, and shorter T < inf > 1/2 < /inf > than men (all ps < 0.04). The rates of BNA were significantly correlated with ratings of smoking motivations of getting a 'rush', getting relaxing effects and marginally with alleviation of craving. These results do not provide strong support for the putative role of menthol in enhancing BNA, although further studies should explore the apparent effect of menthol on BNA in men. Fast BNA during smoking and preference of sensory properties of menthol cigarettes may independently or jointly contribute to smoking dependence among women.

Authors
Zuo, Y; Mukhin, AG; Garg, S; Nazih, R; Behm, FM; Garg, PK; Rose, JE
MLA Citation
Zuo, Y, Mukhin, AG, Garg, S, Nazih, R, Behm, FM, Garg, PK, and Rose, JE. "Sex-specific effects of cigarette mentholation on brain nicotine accumulation and smoking behavior." Neuropsychopharmacology 40.4 (January 1, 2015): 884-892.
Source
scopus
Published In
Neuropsychopharmacology (Nature)
Volume
40
Issue
4
Publish Date
2015
Start Page
884
End Page
892
DOI
10.1038/npp.2014.263

Nicotine and non-nicotine smoking factors differentially modulate craving, withdrawal and cerebral blood flow as measured with arterial spin labeling.

Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation.

Authors
Addicott, MA; Froeliger, B; Kozink, RV; Van Wert, DM; Westman, EC; Rose, JE; McClernon, FJ
MLA Citation
Addicott, MA, Froeliger, B, Kozink, RV, Van Wert, DM, Westman, EC, Rose, JE, and McClernon, FJ. "Nicotine and non-nicotine smoking factors differentially modulate craving, withdrawal and cerebral blood flow as measured with arterial spin labeling." Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 39.12 (November 2014): 2750-2759.
PMID
24820539
Source
epmc
Published In
Neuropsychopharmacology (Nature)
Volume
39
Issue
12
Publish Date
2014
Start Page
2750
End Page
2759
DOI
10.1038/npp.2014.108

Combination treatment with varenicline and bupropion in an adaptive smoking cessation paradigm.

The authors assessed the efficacy and safety of combination treatment with varenicline and sustained-release bupropion for smokers who, based on an assessment of initial smoking reduction prior to the quit date, were deemed unlikely to achieve abstinence using nicotine patch treatment.In a randomized, double-blind, parallel-group adaptive treatment trial, the authors identified 222 cigarette smokers who failed to show a reduction of more than 50% in smoking after 1 week of nicotine patch treatment. Smokers were randomly assigned to receive 12 weeks of varenicline plus bupropion or varenicline plus placebo. The primary outcome measure was continuous smoking abstinence at weeks 8-11 after the target quit date.Both treatments were well tolerated. Participants who received the combination treatment had a significantly higher abstinence rate than those who received varenicline plus placebo (39.8% compared with 25.9%; odds ratio=1.89; 95% CI=1.07, 3.35). Combination treatment had a significantly greater effect on abstinence rate in male smokers (odds ratio=4.26; 95% CI=1.73, 10.49) than in female smokers (odds ratio=0.94; 95% CI=0.43, 2.05). It also had a significantly greater effect in highly nicotine-dependent smokers (odds ratio=3.51, 95% CI=1.64, 7.51) than in smokers with lower levels of dependence (odds ratio=0.71, 95% CI=0.28, 1.80).Among smokers who did not show a sufficient initial response to prequit nicotine patch treatment, combination treatment with varenicline and bupropion proved more efficacious than varenicline alone for male smokers and for smokers with a high degree of nicotine dependence.

Authors
Rose, JE; Behm, FM
MLA Citation
Rose, JE, and Behm, FM. "Combination treatment with varenicline and bupropion in an adaptive smoking cessation paradigm." The American journal of psychiatry 171.11 (November 2014): 1199-1205.
PMID
24934962
Source
epmc
Published In
American Journal of Psychiatry
Volume
171
Issue
11
Publish Date
2014
Start Page
1199
End Page
1205
DOI
10.1176/appi.ajp.2014.13050595

IV nicotine self-administration in rats using a consummatory operant licking response: sensitivity to serotonergic, glutaminergic and histaminergic drugs.

Tobacco smoking is characterized by repeated self-administration of nicotine by placing the cigarette in the mouth. The repeated hand-to-mouth self-administration is essentially a consummatory act. We recently developed a paradigm in which rats lick one of two spouts to trigger intravenous (IV) delivery of nicotine, which combines a consummatory act with rapid delivery of nicotine to model the act of tobacco smoking. We have found that rats will lick hundreds of times per nicotine infusion. In the current study, using the operant licking nicotine self-administration model with young adult Sprague-Dawley rats (0.03mg/kg/infusion of nicotine), we tested the effect of antagonists of H1 histamine receptors pyrilamine, serotonin (5HT) type 2 receptors ketanserin and N-methyl-d-aspartate (NMDA) glutamate receptors with d-cycloserine as well as an agonist of 5HT2c receptors lorcaserin, in dose ranges that we have found in previous studies to significantly reduce IV nicotine self-administration with the operant lever press operand. The H1 antagonist pyrilamine significantly reduced operant licking for nicotine self-administration. Pyrilamine caused significant reductions in the operant licking paradigm at lower doses (10 and 20mg/kg) than those we previously observed to affect responding in the operant lever press paradigm. In contrast, the 5HT2A and C antagonist ketanserin did not show an effect of reducing nicotine self-administration in the same dose range we had found in a previous study to significantly reduce operant lever press nicotine self-administration. The 5HT2C agonist lorcaserin significantly decreased nicotine self-administration in the licking paradigm at the same dose threshold as with lever press responding. The NMDA glutamate partial agonist d-cycloserine did not produce any change in nicotine self-administration with the licking operand, in contrast to its effect on the classic lever-pressing task. The rat model incorporating consummatory aspects of tobacco addiction can provide distinct and potentially more relevant information concerning possible new avenues of treatment to combat tobacco addiction.

Authors
Cousins, V; Rose, JE; Levin, ED
MLA Citation
Cousins, V, Rose, JE, and Levin, ED. "IV nicotine self-administration in rats using a consummatory operant licking response: sensitivity to serotonergic, glutaminergic and histaminergic drugs." Progress in neuro-psychopharmacology & biological psychiatry 54 (October 2014): 200-205.
PMID
24953434
Source
epmc
Published In
Progress in Neuro-Psychopharmacology & Biological Psychiatry
Volume
54
Publish Date
2014
Start Page
200
End Page
205
DOI
10.1016/j.pnpbp.2014.06.004

Brain nicotinic acetylcholine receptor availability and response to smoking cessation treatment: a randomized trial.

Cigarette smoking leads to upregulation of nicotinic acetylcholine receptors (nAChRs) in the human brain, including the common α4β2* nAChR subtype. While subjective aspects of tobacco dependence have been extensively examined as predictors of quitting smoking with treatment, no studies to our knowledge have yet reported the relationship between the extent of pretreatment upregulation of nAChRs and smoking cessation.To determine whether the degree of nAChR upregulation in smokers predicts quitting with a standard course of treatment.Eighty-one tobacco-dependent cigarette smokers (volunteer sample) underwent positron emission tomographic (PET) scanning of the brain with the radiotracer 2-FA followed by 10 weeks of double-blind, placebo-controlled treatment with nicotine patch (random assignment). Pretreatment specific binding volume of distribution (VS/fP) on PET images (a value that is proportional to α4β2* nAChR availability) was determined for 8 brain regions of interest, and participant-reported ratings of nicotine dependence, craving, and self-efficacy were collected. Relationships between these pretreatment measures, treatment type, and outcome were then determined. The study took place at academic PET and clinical research centers.Posttreatment quit status after treatment, defined as a participant report of 7 or more days of continuous abstinence and an exhaled carbon monoxide level of 3 ppm or less.Smokers with lower pretreatment VS/fP values (a potential marker of less severe nAChR upregulation) across all brain regions studied were more likely to quit smoking (multivariate analysis of covariance, F8,69 = 4.5; P < .001), regardless of treatment group assignment. Furthermore, pretreatment average VS/fP values provided additional predictive power for likelihood of quitting beyond the self-report measures (stepwise binary logistic regression, likelihood ratio χ21 = 19.8; P < .001).Smokers with less upregulation of available α4β2* nAChRs have a greater likelihood of quitting with treatment than smokers with more upregulation. In addition, the biological marker studied here provided additional predictive power beyond subjectively rated measures known to be associated with smoking cessation outcome. While the costly, time-consuming PET procedure used here is not likely to be used clinically, simpler methods for examining α4β2* nAChR upregulation could be tested and applied in the future to help determine which smokers need more intensive and/or lengthier treatment.clinicaltrials.gov Identifier: NCT01526005.

Authors
Brody, AL; Mukhin, AG; Mamoun, MS; Luu, T; Neary, M; Liang, L; Shieh, J; Sugar, CA; Rose, JE; Mandelkern, MA
MLA Citation
Brody, AL, Mukhin, AG, Mamoun, MS, Luu, T, Neary, M, Liang, L, Shieh, J, Sugar, CA, Rose, JE, and Mandelkern, MA. "Brain nicotinic acetylcholine receptor availability and response to smoking cessation treatment: a randomized trial." JAMA psychiatry 71.7 (July 2014): 797-805.
PMID
24850280
Source
epmc
Published In
JAMA Psychiatry
Volume
71
Issue
7
Publish Date
2014
Start Page
797
End Page
805
DOI
10.1001/jamapsychiatry.2014.138

Combination Treatment With Varenicline and Bupropion in an Adaptive Smoking Cessation Paradigm

OBJECTIVE The authors assessed the efficacy and safety of combination treatment with varenicline and sustained-release bupropion for smokers who, based on an assessment of initial smoking reduction prior to the quit date, were deemed unlikely to achieve abstinence using nicotine patch treatment. METHOD In a randomized, double-blind, parallel-group adaptive treatment trial, the authors identified 222 cigarette smokers who failed to show a reduction of more than 50% in smoking after 1 week of nicotine patch treatment. Smokers were randomly assigned to receive 12 weeks of varenicline plus bupropion or varenicline plus placebo. The primary outcome measure was continuous smoking abstinence at weeks 8-11 after the target quit date. RESULTS Both treatments were well tolerated. Participants who received the combination treatment had a significantly higher abstinence rate than those who received varenicline plus placebo (39.8% compared with 25.9%; odds ratio=1.89; 95% CI=1.07, 3.35). Combination treatment had a significantly greater effect on abstinence rate in male smokers (odds ratio=4.26; 95% CI=1.73, 10.49) than in female smokers (odds ratio=0.94; 95% CI=0.43, 2.05). It also had a significantly greater effect in highly nicotine-dependent smokers (odds ratio=3.51, 95% CI=1.64, 7.51) than in smokers with lower levels of dependence (odds ratio=0.71, 95% CI=0.28, 1.80). CONCLUSIONS Among smokers who did not show a sufficient initial response to prequit nicotine patch treatment, combination treatment with varenicline and bupropion proved more efficacious than varenicline alone for male smokers and for smokers with a high degree of nicotine dependence.

Authors
Rose, JE; Behm, FM
MLA Citation
Rose, JE, and Behm, FM. "Combination Treatment With Varenicline and Bupropion in an Adaptive Smoking Cessation Paradigm." American Journal of Psychiatry (June 17, 2014).
Website
http://hdl.handle.net/10161/9020
Source
manual
Published In
American Journal of Psychiatry
Publish Date
2014
DOI
10.1176/appi.ajp.2014

Differential effects of non-nicotine tobacco constituent compounds on nicotine self-administration in rats.

Tobacco smoking has been shown to be quite addictive in people. However, nicotine itself is a weak reinforcer compared to other commonly abused drugs, leading speculation that other factors contribute to the high prevalence of tobacco addiction in the human population. In addition to nicotine, there are over 5000 chemical compounds that have been identified in tobacco smoke, and more work is needed to ascertain their potential contributions to tobacco's highly addictive properties, or as potential candidates for smoking cessation treatment. In this study, we examined seven non-nicotine tobacco constituent compounds (anabasine, anatabine, nornicotine, myosmine, harmane, norharmane, and tyramine) for their effects on nicotine self-administration behavior in rats. Young adult female Sprague-Dawley rats were allowed to self-administer nicotine (0.03 mg/kg/50 μl infusion) under a fixed ratio-1 schedule of reinforcement. Each self-administration session lasted 45 min. Doses of each tobacco constituent compound were administered subcutaneously 10 min prior to the start of each session in a repeated measures, counterbalanced order two times. Anabasine displayed a biphasic dose-effect function. Pretreatment with 0.02 mg/kg anabasine resulted in a 25% increase in nicotine self-administration, while 2.0mg/kg of anabasine reduced nicotine infusions per session by over 50%. Pretreatment with 2.0mg/kg anatabine also significantly reduced nicotine self-administration by nearly half. These results suggest that some non-nicotine tobacco constituents may enhance or reduce nicotine's reinforcing properties. Also, depending upon the appropriate dose, some of these compounds may also serve as potential smoking cessation agents.

Authors
Hall, BJ; Wells, C; Allenby, C; Lin, MY; Hao, I; Marshall, L; Rose, JE; Levin, ED
MLA Citation
Hall, BJ, Wells, C, Allenby, C, Lin, MY, Hao, I, Marshall, L, Rose, JE, and Levin, ED. "Differential effects of non-nicotine tobacco constituent compounds on nicotine self-administration in rats." Pharmacology, biochemistry, and behavior 120 (May 2014): 103-108.
PMID
24560911
Source
epmc
Published In
Pharmacology Biochemistry and Behavior
Volume
120
Publish Date
2014
Start Page
103
End Page
108
DOI
10.1016/j.pbb.2014.02.011

Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances

Genotype scores that predict relevant clinical outcomes may detect other disease features and help direct prevention efforts. We report data that validate a previously established v1.0 smoking cessation quit success genotype score and describe striking differences in the score in individuals who display differing developmental trajectories of use of common addictive substances. In a cessation study, v1.0 genotype scores predicted ability to quit with P=0.00056 and area under receiver-operating characteristic curve 0.66. About 43% vs 13% quit in the upper vs lower genotype score terciles. Latent class growth analyses of a developmentally assessed sample identified three latent classes based on substance use. Higher v1.0 scores were associated with (a) higher probabilities of participant membership in a latent class that displayed low use of common addictive substances during adolescence (P=0.0004) and (b) lower probabilities of membership in a class that reported escalating use (P=0.001). These results indicate that: ( a) we have identified genetic predictors of smoking cessation success, (b) genetic influences on quit success overlap with those that influence the rate at which addictive substance use is taken up during adolescence and (c) individuals at genetic risk for both escalating use of addictive substances and poor abilities to quit may provide especially urgent focus for prevention efforts. © 2014 Macmillan Publishers Limited.

Authors
Uhl, GR; Walther, D; Musci, R; Fisher, C; Anthony, JC; Storr, CL; Behm, FM; Eaton, WW; Ialongo, N; Rose, JE
MLA Citation
Uhl, GR, Walther, D, Musci, R, Fisher, C, Anthony, JC, Storr, CL, Behm, FM, Eaton, WW, Ialongo, N, and Rose, JE. "Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances." Molecular Psychiatry 19.1 (January 1, 2014): 50-54.
Source
scopus
Published In
Molecular Psychiatry
Volume
19
Issue
1
Publish Date
2014
Start Page
50
End Page
54
DOI
10.1038/mp.2012.155

Nicotine and non-nicotine smoking factors differentially modulate craving, withdrawal and cerebral blood flow as measured with arterial spin labeling

© 2014 American College of Neuropsychopharmacology. All rights reserved.Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation.

Authors
Addicott, MA; Froeliger, B; Kozink, RV; Wert, DMV; Westman, EC; Rose, JE; McClernon, FJ
MLA Citation
Addicott, MA, Froeliger, B, Kozink, RV, Wert, DMV, Westman, EC, Rose, JE, and McClernon, FJ. "Nicotine and non-nicotine smoking factors differentially modulate craving, withdrawal and cerebral blood flow as measured with arterial spin labeling." Neuropsychopharmacology 39.12 (2014): 2750-2759.
Source
scival
Published In
Neuropsychopharmacology (Nature)
Volume
39
Issue
12
Publish Date
2014
Start Page
2750
End Page
2759
DOI
10.1038/npp.2014.108

A common biological basis of obesity and nicotine addiction

Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34 216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 × 10 -7 ). These findings replicate in a second large data set (N=127 274, thereof 76 242 smokers) for both SI (P=1.2 × 10 -5 ) and CPD (P=9.3 × 10 -5 ). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity. © 2013 Macmillan Publishers Limited.

Authors
Thorgeirsson, TE; Gudbjartsson, DF; Sulem, P; Besenbacher, S; Styrkarsdottir, U; Thorleifsson, G; Walters, GB; Furberg, H; Sullivan, PF; Marchini, J; McCarthy, MI; Steinthorsdottir, V; Thorsteinsdottir, U; Stefansson, K; Surakka, I; Vink, JM; Amin, N; Geller, F; Rafnar, T; Esko, T; Walter, S; Gieger, C; Rawal, R; Mangino, M; Prokopenko, I; Mägi, R; Keskitalo, K; Gudjonsdottir, IH; Gretarsdottir, S; Stefansson, H; Aulchenko, YS; Nelis, M; Aben, KK; Den Heijer, M; Soranzo, N; Valdes, AM et al.
MLA Citation
Thorgeirsson, TE, Gudbjartsson, DF, Sulem, P, Besenbacher, S, Styrkarsdottir, U, Thorleifsson, G, Walters, GB, Furberg, H, Sullivan, PF, Marchini, J, McCarthy, MI, Steinthorsdottir, V, Thorsteinsdottir, U, Stefansson, K, Surakka, I, Vink, JM, Amin, N, Geller, F, Rafnar, T, Esko, T, Walter, S, Gieger, C, Rawal, R, Mangino, M, Prokopenko, I, Mägi, R, Keskitalo, K, Gudjonsdottir, IH, Gretarsdottir, S, Stefansson, H, Aulchenko, YS, Nelis, M, Aben, KK, Den Heijer, M, Soranzo, N, and Valdes, AM et al. "A common biological basis of obesity and nicotine addiction." Translational Psychiatry 3 (November 4, 2013): 1-7.
Source
scopus
Published In
Translational Psychiatry
Volume
3
Publish Date
2013
Start Page
1
End Page
7
DOI
10.1038/tp.2013.81

Role of insular cortex D₁ and D₂ dopamine receptors in nicotine self-administration in rats.

The insular cortex has been associated with the processing of rewarding stimuli and with the neural bases of drug addiction. Ischemic damage to the insula has been associated with decreased desire to smoke cigarettes. Which component of insular function is involved in the neural basis of cigarette smoking is not clear. Dopamine systems are crucial for the reinforcing value of addictive drugs. The DA projection from the ventral tegmental area to the nucleus accumbens (NAc) has been shown to be a vital pathway for the primary reinforcement caused by taking a variety of abused drugs. In the current set of studies, the roles of D₁ and D₂ receptors in the insular cortex in the self-administration of nicotine by rats were assessed. Adult female Sprague-Dawley rats were fitted with jugular catheters and given access to self-administer nicotine. Bilateral local infusion cannulae were implanted into the agranular insular cortex to locally administer D₁ and D₂ antagonists (SCH-23390 and haloperidol). Acute local infusions of the D₁ antagonist SCH-23390 into the insula (1-2 μg/side) significantly decreased nicotine self-administration by more than 50%. Repeated infusions of SCH-23390 into the agranular insula caused continuing decreases in nicotine self-administration without signs of tolerance. In contrast, local infusions of the D₂ antagonist haloperidol 0.5-2 μg/side did not have any discernable effect on nicotine self-administration. These studies show the importance of DA D₁ systems in the insula for nicotine reward.

Authors
Kutlu, MG; Burke, D; Slade, S; Hall, BJ; Rose, JE; Levin, ED
MLA Citation
Kutlu, MG, Burke, D, Slade, S, Hall, BJ, Rose, JE, and Levin, ED. "Role of insular cortex D₁ and D₂ dopamine receptors in nicotine self-administration in rats." Behav Brain Res 256 (November 1, 2013): 273-278.
PMID
23948214
Source
pubmed
Published In
Behavioural Brain Research
Volume
256
Publish Date
2013
Start Page
273
End Page
278
DOI
10.1016/j.bbr.2013.08.005

Adapting Smoking Cessation Treatment According to Initial Response to Precessation Nicotine Patch

Authors
Rose, JE; Behm, FM
MLA Citation
Rose, JE, and Behm, FM. "Adapting Smoking Cessation Treatment According to Initial Response to Precessation Nicotine Patch." AMERICAN JOURNAL OF PSYCHIATRY 170.8 (August 2013): 860-867.
PMID
23640009
Source
wos-lite
Published In
American Journal of Psychiatry
Volume
170
Issue
8
Publish Date
2013
Start Page
860
End Page
867
DOI
10.1176/appi.ajp.2013.12070919

Biomarkers for smoking cessation.

One way to enhance therapeutic development is through the identification and development of evaluative tools such as biomarkers. This review focuses on putative diagnostic, pharmacodynamic, and predictive biomarkers for smoking cessation. These types of biomarkers may be used to more accurately diagnose a disease, personalize treatment, identify novel targets for drug discovery, and enhance the efficiency of drug development. Promising biomarkers are presented across a range of approaches including metabolism, genetics, and neuroimaging. A preclinical viewpoint is also offered, as are analytical considerations and a regulatory perspective summarizing a pathway toward biomarker qualification.

Authors
Bough, KJ; Lerman, C; Rose, JE; McClernon, FJ; Kenny, PJ; Tyndale, RF; David, SP; Stein, EA; Uhl, GR; Conti, DV; Green, C; Amur, S
MLA Citation
Bough, KJ, Lerman, C, Rose, JE, McClernon, FJ, Kenny, PJ, Tyndale, RF, David, SP, Stein, EA, Uhl, GR, Conti, DV, Green, C, and Amur, S. "Biomarkers for smoking cessation." Clin Pharmacol Ther 93.6 (June 2013): 526-538. (Review)
PMID
23588313
Source
pubmed
Published In
Clinical Pharmacology & Therapeutics (Nature)
Volume
93
Issue
6
Publish Date
2013
Start Page
526
End Page
538
DOI
10.1038/clpt.2013.57

Biomarkers for smoking cessation

One way to enhance therapeutic development is through the identification and development of evaluative tools such as biomarkers. This review focuses on putative diagnostic, pharmacodynamic, and predictive biomarkers for smoking cessation. These types of biomarkers may be used to more accurately diagnose a disease, personalize treatment, identify novel targets for drug discovery, and enhance the efficiency of drug development. Promising biomarkers are presented across a range of approaches including metabolism, genetics, and neuroimaging. A preclinical viewpoint is also offered, as are analytical considerations and a regulatory perspective summarizing a pathway toward biomarker qualification.

Authors
Bough, KJ; Lerman, C; Rose, JE; McClernon, FJ; Kenny, PJ; Tyndale, RF; David, SP; Stein, EA; Uhl, GR; Conti, DV; Green, C; Amur, S
MLA Citation
Bough, KJ, Lerman, C, Rose, JE, McClernon, FJ, Kenny, PJ, Tyndale, RF, David, SP, Stein, EA, Uhl, GR, Conti, DV, Green, C, and Amur, S. "Biomarkers for smoking cessation." Clinical Pharmacology and Therapeutics 93.6 (2013): 526-538.
Source
scival
Published In
Clinical Pharmacology & Therapeutics (Nature)
Volume
93
Issue
6
Publish Date
2013
Start Page
526
End Page
538
DOI
10.1038/clpt.2013.57

Neuroanatomical evidence for a putative autocrine/paracrine signaling system involving nicotinic acetylcholine receptors, purinergic receptors, and nitric oxide synthase in the airways.

Nicotine in tobacco smoke is thought to stimulate sensory nerve fibers by receptors that are located on airway epithelial cells and on terminal branches of C-fiber afferents, but the exact neurochemical substrate that mediates the sensory effects of nicotine associated with cigarette smoking is not clear. ATP and nitric oxide (NO) have both been implicated in lung responsiveness to airborne chemicals such as nicotine. However, the neuroanatomical and functional relationships between nicotinic acetylcholine receptors (nAChRs), purinergic signaling, and NO are not known, and the main source of NO in the airways is not clear. In the present study, we performed RT-PCR to confirm the presence of mRNA for all three isoforms of nitric oxide synthase (NOS), neuronal (n-NOS), endothelial (e-NOS), and inducible (i-NOS), in the lung. Sequential double labeling was performed to assess the site of expression of the different NOS isoforms with respect to nAChRs and purinergic receptors (P2X3R) of the intrapulmonary airways. RT-PCR confirmed the presence of n-NOS, e-NOS, and i-NOS in the lung, and immunohistochemical studies verified their expression by epithelial cells at all levels of the intrapulmonary airways, including the terminal and respiratory bronchioles. Sequential double labeling demonstrated coexpression of n-NOS and/or i-NOS with nAChR- and P2X3R-expressing cells. These neuroanatomical findings suggest that bronchial epithelial cells may be a primary source of NO in the intrapulmonary airways and that the production and release of NO may be regulated by an autocrine/paracrine signaling system involving nAChRs and P2X3Rs.

Authors
Rose, JE; Dehkordi, O; Fatemi, M; Raghupathi, R; Millis, RM; Jayam-Trouth, A
MLA Citation
Rose, JE, Dehkordi, O, Fatemi, M, Raghupathi, R, Millis, RM, and Jayam-Trouth, A. "Neuroanatomical evidence for a putative autocrine/paracrine signaling system involving nicotinic acetylcholine receptors, purinergic receptors, and nitric oxide synthase in the airways." J Neurosci Res 90.4 (April 2012): 849-859.
PMID
22420037
Source
pubmed
Published In
Journal of Neuroscience Research
Volume
90
Issue
4
Publish Date
2012
Start Page
849
End Page
859
DOI
10.1002/jnr.22817

Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances

Genotype scores that predict relevant clinical outcomes may detect other disease features and help direct prevention efforts. We report data that validate a previously established v1.0 smoking cessation quit success genotype score and describe striking differences in the score in individuals who display differing developmental trajectories of use of common addictive substances. In a cessation study, v1.0 genotype scores predicted ability to quit with P=0.00056 and area under receiver-operating characteristic curve 0.66. About 43% vs 13% quit in the upper vs lower genotype score terciles. Latent class growth analyses of a developmentally assessed sample identified three latent classes based on substance use. Higher v1.0 scores were associated with (a) higher probabilities of participant membership in a latent class that displayed low use of common addictive substances during adolescence (P=0.0004) and (b) lower probabilities of membership in a class that reported escalating use (P=0.001). These results indicate that: (a) we have identified genetic predictors of smoking cessation success, (b) genetic influences on quit success overlap with those that influence the rate at which addictive substance use is taken up during adolescence and (c) individuals at genetic risk for both escalating use of addictive substances and poor abilities to quit may provide especially urgent focus for prevention efforts.Molecular Psychiatry advance online publication, 6 November 2012; doi:10.1038/mp.2012.155.

Authors
Uhl, GR; Walther, D; Musci, R; Fisher, C; Anthony, JC; Storr, CL; Behm, FM; Eaton, WW; Ialongo, N; Rose, JE
MLA Citation
Uhl, GR, Walther, D, Musci, R, Fisher, C, Anthony, JC, Storr, CL, Behm, FM, Eaton, WW, Ialongo, N, and Rose, JE. "Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances." Molecular Psychiatry (2012).
PMID
23128154
Source
scival
Published In
Molecular Psychiatry
Publish Date
2012
DOI
10.1038/mp.2012.155

Neuronal expression of bitter taste receptors and downstream signaling molecules in the rat brainstem

Previous studies have shown that molecules of the taste transduction pathway may serve as biochemical markers for chemoreceptive cells in respiratory and gastrointestinal tracts. In this study, we tested the hypothesis that brainstem neurons contain signaling molecules similar to those in taste buds which may sense the chemical composition of brain extracellular fluids. We used the reverse transcription polymerase chain reaction (RT-PCR), Western blot and immunohistochemical techniques to evaluate presence of different bitter-responsive type 2 taste receptors (T2Rs), their associated G-protein α-gustducin, the downstream signaling molecules phospholipase C isoform β2 (PLC-β2) and transient receptor potential melastatin 5 (TRPM5) in the brainstem of rats. RT-PCR confirmed the mRNA coding for α-gustducin, PLC-β2, TRPM5 and rT2R1 but not that of rT2R16, rT2R26 and rT2R38 in the medulla oblongata. Western blotting confirmed the presence of α-gustducin at the protein level in rat brainstem. Immunohistochemistry identified cells expressing α-gustducin and PLC-β2 at multiple cardiorespiratory and CO2/H chemosensory sites, including rostral ventral medulla, facial, parapyramidal, solitary tract, hypoglossal and raphe nuclei. In the medullary raphe, α-gustducin and PLC-β2 were colocalized with a subpopulation of tryptophan hydroxylase (TPH)-immunoreactive serotonergic neurons, a subset of which has respiratory CO2/H chemosensitivity. Presence of the T2R1 gene and other genes and proteins of the bitter taste transduction pathway in the brainstem implies additional functions for taste receptors and their effector molecules apart from their gustatory function. © 2012 Elsevier B.V. All rights reserved.

Authors
Dehkordi, O; Rose, JE; Fatemi, M; Allard, JS; Balan, KV; Young, JK; Fatima, S; Millis, RM; Jayam-Trouth, A
MLA Citation
Dehkordi, O, Rose, JE, Fatemi, M, Allard, JS, Balan, KV, Young, JK, Fatima, S, Millis, RM, and Jayam-Trouth, A. "Neuronal expression of bitter taste receptors and downstream signaling molecules in the rat brainstem." Brain Research 1475 (2012): 1-10.
PMID
22836012
Source
scival
Published In
Brain Research
Volume
1475
Publish Date
2012
Start Page
1
End Page
10
DOI
10.1016/j.brainres.2012.07.038

Repetitive transcranial magnetic stimulation of the superior frontal gyrus modulates craving for cigarettes.

BACKGROUND: Previous functional magnetic resonance imaging studies have shown strong correlations between cue-elicited craving for cigarettes and activation of the superior frontal gyrus (SFG). Repetitive transcranial magnetic stimulation (rTMS) offers a noninvasive means to reversibly affect brain cortical activity, which can be applied to testing hypotheses about the causal role of SFG in modulating craving. METHODS: Fifteen volunteer smokers were recruited to investigate the effects of rTMS on subjective responses to smoking versus neutral cues and to controlled presentations of cigarette smoke. On different days, participants were exposed to three conditions: 1) high-frequency (10 Hz) rTMS directed at the SFG; 2) low-frequency (1 Hz) rTMS directed at the SFG; and 3) low-frequency (1 Hz) rTMS directed at the motor cortex (control condition). RESULTS: Craving ratings in response to smoking versus neutral cues were differentially affected by the 10-Hz versus 1-Hz SFG condition. Craving after smoking cue presentations was elevated in the 10-Hz SFG condition, whereas craving after neutral cue presentations was reduced. Upon smoking in the 10-Hz SFG condition, ratings of immediate craving reduction as well as the intensity of interoceptive airway sensations were also attenuated. CONCLUSIONS: These results support the view that the SFG plays a role in modulating craving reactivity; moreover, the results suggest that the SFG plays a role in both excitatory and inhibitory influences on craving, consistent with prior research demonstrating the role of the prefrontal cortex in the elicitation as well as inhibition of drug-seeking behaviors.

Authors
Rose, JE; McClernon, FJ; Froeliger, B; Behm, FM; Preud'homme, X; Krystal, AD
MLA Citation
Rose, JE, McClernon, FJ, Froeliger, B, Behm, FM, Preud'homme, X, and Krystal, AD. "Repetitive transcranial magnetic stimulation of the superior frontal gyrus modulates craving for cigarettes." Biol Psychiatry 70.8 (October 15, 2011): 794-799.
PMID
21762878
Source
pubmed
Published In
Biological Psychiatry
Volume
70
Issue
8
Publish Date
2011
Start Page
794
End Page
799
DOI
10.1016/j.biopsych.2011.05.031

Lorcaserin, a 5-HT2C agonist, decreases nicotine self-administration in female rats.

Lorcaserin, a selective 5-hydroxytryptamine(2C) (5-HT(2C)) agonist, has been shown to facilitate weight loss in obese populations. It was assessed for its efficacy in reducing nicotine self-administration in young adult female Sprague-Dawley rats. The effect of short-term doses (subcutaneous) on nicotine self-administration (0.03 mg/kg per infusion) with a fixed ratio 1 schedule was assessed in 3-h sessions. Short-term lorcaserin doses (0.3125-20 mg/kg) were administered in a counterbalanced order. Significant reduction of nicotine self-administration was achieved with all of the short-term doses in this range. Tests of lorcaserin on locomotor activity detected prominent sedative effects at doses greater than 1.25 mg/kg with more modest transient effects seen at 0.625 to 1.25 mg/kg. Long-term effects of lorcaserin on locomotor activity were tested with repeated injections with 0.625 mg/kg lorcaserin 10 times over 2 weeks. This low lorcaserin dose did not cause an overall change in locomotor activity relative to that of saline-injected controls. Long-term lorcaserin (0.625 mg/kg) significantly reduced nicotine self-administration over a 2-week period of repeated injections. Long-term lorcaserin at this same dose had no significant effects on food self-administration over the same 2-week period of repeated injections. These studies support development of the 5-HT(2C) agonist lorcaserin to aid tobacco smoking cessation.

Authors
Levin, ED; Johnson, JE; Slade, S; Wells, C; Cauley, M; Petro, A; Rose, JE
MLA Citation
Levin, ED, Johnson, JE, Slade, S, Wells, C, Cauley, M, Petro, A, and Rose, JE. "Lorcaserin, a 5-HT2C agonist, decreases nicotine self-administration in female rats." J Pharmacol Exp Ther 338.3 (September 2011): 890-896.
PMID
21636655
Source
pubmed
Published In
The Journal of pharmacology and experimental therapeutics
Volume
338
Issue
3
Publish Date
2011
Start Page
890
End Page
896
DOI
10.1124/jpet.111.183525

D-cycloserine selectively decreases nicotine self-administration in rats with low baseline levels of response.

Expanding the variety of treatments available to aid smoking cessation will allow the treatments to be customized to particular types of smokers. The key is to understand which subpopulations of smokers respond best to which treatment. This study used adult female Sprague-Dawley rats to evaluate the efficacy of D-cycloserine, a partial NMDA glutamate receptor agonist, in reducing nicotine self-administration. Rats were trained to self-administer nicotine (0.03 mg/kg/infusion, i.v.) via operant lever response (FR1) with a secondary visual reinforcer. Two studies of D-cycloserine effects on nicotine self-administration were conducted: an acute dose-effect study (0, 10, 20 and 40 mg/kg, s.c.) and a chronic study with 40 mg/kg given before each test session for two weeks. Effects on rats with low or high pretreatment baseline levels of nicotine self-administration were assessed. In the acute study there was a significant interaction of D-cycloserine×baseline level of nicotine self-administration. In the low baseline group, 10 mg/kg D-cycloserine significantly decreased nicotine self-administration. In the high baseline group, 40 mg/kg significantly increased nicotine self-administration. In the repeated injection study, there was also a significant interaction of d-cycloserine×baseline level of nicotine self-administration. Chronic D-cycloserine significantly reduced nicotine self-administration selectively in rats with low baseline nicotine use, but was ineffective with the rats with higher levels of baseline nicotine self-administration. NMDA glutamate treatments may be particularly useful in helping lighter smokers successfully quit smoking, highlighting the need for diverse treatments for different types of smokers.

Authors
Levin, ED; Slade, S; Wells, C; Petro, A; Rose, JE
MLA Citation
Levin, ED, Slade, S, Wells, C, Petro, A, and Rose, JE. "D-cycloserine selectively decreases nicotine self-administration in rats with low baseline levels of response." Pharmacol Biochem Behav 98.2 (April 2011): 210-214.
PMID
21192967
Source
pubmed
Published In
Pharmacology, Biochemistry and Behavior
Volume
98
Issue
2
Publish Date
2011
Start Page
210
End Page
214
DOI
10.1016/j.pbb.2010.12.023

Histamine H(1) antagonist treatment with pyrilamine reduces nicotine self-administration in rats.

Nicotine has been definitively shown to be critically involved in the neural bases of tobacco addiction. However, nicotine releases a wide variety of neurotransmitters. Nicotine-induced dopamine release has been shown to play a key role in facilitating nicotine self-administration. Other transmitter systems may also play important roles in the pharmacological effects of nicotine and may provide important leads for combating nicotine self-administration. Clozapine, an antipsychotic drug, which blocks a variety of different transmitter receptors including serotonin 5HT(2) and histamine H(1) receptors, has been found to decrease smoking. Previously we found that the serotonin 5HT(2) antagonist, ketanserin, significantly reduced nicotine self-administration. In the current study, we assessed histamine H(1) receptor interaction with nicotine self-administration. Young adult female Sprague-Dawley rats were fitted with IV catheters and trained to self-administer nicotine (0.03mg/kg/infusion). Acute doses of 40mg/kg of pyrilamine, a histamine H(1) antagonist, significantly reduced nicotine self-administration. We also found that repeated injections (20mg/kg) or chronic infusion via osmotic minipumps (50mg/kg/day) of pyrilamine also significantly decreased nicotine self-administration. The peripherally restricted H(1) antagonist ebastine was ineffective in reducing nicotine self-administration, pointing to central H(1) receptor blockade as key for the effectiveness of pyrilamine. H(1) antagonists may be a promising avenue to explore for new treatments to aid smoking cessation.

Authors
Levin, ED; Slade, S; Wells, C; Pruitt, M; Cousins, V; Cauley, M; Petro, A; Hampton, D; Rose, J
MLA Citation
Levin, ED, Slade, S, Wells, C, Pruitt, M, Cousins, V, Cauley, M, Petro, A, Hampton, D, and Rose, J. "Histamine H(1) antagonist treatment with pyrilamine reduces nicotine self-administration in rats." Eur J Pharmacol 650.1 (January 10, 2011): 256-260.
PMID
20951696
Source
pubmed
Published In
European Journal of Pharmacology
Volume
650
Issue
1
Publish Date
2011
Start Page
256
End Page
260
DOI
10.1016/j.ejphar.2010.10.013

Menthol preference among smokers: Association with TRPA1 variants

Introduction: Preference for smoking menthol cigarettes differs from individual to individual and population to population in ways that may provide higher levels of nicotine intake and contribute to smoking's morbidity and mortality. Menthol acts at sites that include the transient receptor potential (TRP) A1 channel that is expressed by nociceptors in the lung and airways, suggesting that individual and population differences in TRPA1 sequences might contribute to observed differences in menthol preference among smokers. Methods: We have thus sought association between menthol preference and common variants in the TRPA1 gene in heavier and lighter European-American smokers. Smokers were recruited for studies of smoking cessation in North Carolina and of substance abuse genetics in Maryland. Results: A common TRPA1 haplotype is defined by 1 missense and 10 intronic single nucleotide polymorphisms that display significant (.006 < p < .05; χ2) association with preference for mentholated cigarettes in heavy smokers (odds ratio ca. 1.3). There are smaller trends in the same direction in lighter smokers. Conclusions: This TRPA1 haplotype provides a novel biological basis for individual differences in menthol preference and possibly for actions of other agents that act at TRPA1. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2011.

Authors
Uhl, GR; Walther, D; Behm, FM; Rose, JE
MLA Citation
Uhl, GR, Walther, D, Behm, FM, and Rose, JE. "Menthol preference among smokers: Association with TRPA1 variants." Nicotine and Tobacco Research 13.12 (2011): 1311-1315.
PMID
21719896
Source
scival
Published In
Nicotine and Tobacco Research (OUP)
Volume
13
Issue
12
Publish Date
2011
Start Page
1311
End Page
1315
DOI
10.1093/ntr/ntr119

Nicotine preloading: The importance of a pre-cessation reduction in smoking behavior

Authors
Rose, JE
MLA Citation
Rose, JE. "Nicotine preloading: The importance of a pre-cessation reduction in smoking behavior." Psychopharmacology 217.3 (2011): 453-454.
PMID
21643677
Source
scival
Published In
Psychopharmacology
Volume
217
Issue
3
Publish Date
2011
Start Page
453
End Page
454
DOI
10.1007/s00213-011-2350-0

Response: a quest and a wager.

Authors
Bevins, R; Kenny, P; Rose, J
MLA Citation
Bevins, R, Kenny, P, and Rose, J. "Response: a quest and a wager." Addiction science & clinical practice 6.1 (2011): 16-17.
PMID
22003418
Source
scival
Published In
Addiction Science and Clinical Practice
Volume
6
Issue
1
Publish Date
2011
Start Page
16
End Page
17

Individualized smoking cessation treatment: Roles for sets of genomic markers

Authors
Uhl, GR; Rose, JE
MLA Citation
Uhl, GR, and Rose, JE. "Individualized smoking cessation treatment: Roles for sets of genomic markers." Personalized Medicine 8.2 (2011): 119-121.
Source
scival
Published In
Personalized medicine
Volume
8
Issue
2
Publish Date
2011
Start Page
119
End Page
121
DOI
10.2217/pme.11.4

Silver acetate interactions with nicotine and non-nicotine smoke components.

Oral topical silver-containing formulations were marketed in the 1970s and 1980s as smoking deterrents, based on the finding that when using such formulations, an unpleasant taste occurs upon smoking. This approach has not been widely adopted, however, in part because of a lack of efficacy data. The advent of new pharmacologic treatments for smoking cessation renews the possibility that such a taste aversion approach may be a useful adjunct to smoking cessation treatment. This study explored the basic mechanistic question of whether topical oral silver acetate solution interacts with nicotine as opposed to non-nicotine smoke constituents. We recruited 20 smoking volunteers to rate nicotine-containing or denicotinized cigarettes, as well as the Nicotrol nicotine vapor inhaler and sham (air) puffs. In two sessions, subjects rated the sensory and hedonic qualities of puffs after rinsing their mouths with either silver acetate solution or deionized water (placebo). Silver acetate relative to placebo solution substantially reduced liking and satisfaction ratings for the usual brand and denicotinized cigarettes; in contrast, for the nicotine inhaler these ratings were unaffected by the silver-based treatment. These results support the conclusion that silver acetate not only renders the taste of cigarette smoke less appealing, but also that the compound appears to interact selectively with non-nicotine smoke constituents. Moreover, these data suggest silver acetate would be compatible with buccal nicotine delivery systems (e.g., nicotine lozenge or gum). Combined use of taste aversion with nicotine replacement therapy could provide the smoker with additional assistance to resist relapse. Further exploration is warranted of the use of silver-based preparations as a short-term adjunct to smoking cessation treatment.

Authors
Rose, JE; Behm, FM; Murugesan, T; McClernon, FJ
MLA Citation
Rose, JE, Behm, FM, Murugesan, T, and McClernon, FJ. "Silver acetate interactions with nicotine and non-nicotine smoke components." Exp Clin Psychopharmacol 18.6 (December 2010): 462-469.
PMID
21186921
Source
pubmed
Published In
Experimental and Clinical Psychopharmacology
Volume
18
Issue
6
Publish Date
2010
Start Page
462
End Page
469
DOI
10.1037/a0021966

Stress alleviation and reward enhancement: two promising targets for relapse prevention.

Authors
Rose, JE
MLA Citation
Rose, JE. "Stress alleviation and reward enhancement: two promising targets for relapse prevention." Biol Psychiatry 68.8 (October 15, 2010): 687-688.
PMID
20888456
Source
pubmed
Published In
Biological Psychiatry
Volume
68
Issue
8
Publish Date
2010
Start Page
687
End Page
688
DOI
10.1016/j.biopsych.2010.08.023

Smoking withdrawal shifts the spatiotemporal dynamics of neurocognition.

Smoking withdrawal is associated with significant deficits in the ability to initiate and maintain attention for extended periods of time (i.e. sustained attention; SA). However, the effects of smoking abstinence on the temporal dynamics of neurocognition during SA have not been evaluated. Twenty adult smokers underwent functional magnetic resonance imaging scans following smoking as usual and after 24-hours abstinence. During scanning they completed a SA task with two levels of task difficulty, designed to measure both sustained (i.e. over the duration of the task) and transient (i.e. event-related) activation. Smoking abstinence significantly decreased task accuracy regardless of task difficulty. Compared to smoking as usual, abstinence resulted in decreased sustained activation in right inferior and middle frontal gyri but increased transient activation across dispersed cortical areas including precuneus and right superior frontal gyrus. Greater task difficulty was associated with even greater transient activation during abstinence in mostly right hemisphere regions including right inferior frontal gyrus. These findings suggest smoking withdrawal shifts the temporal and spatial dynamics of neurocognition from sustained, right prefrontal activation reflecting proactive cognitive control (Braver, Gray & Burgess 2009) to more dispersed and transient activation reflecting reactive control.

Authors
Kozink, RV; Lutz, AM; Rose, JE; Froeliger, B; McClernon, FJ
MLA Citation
Kozink, RV, Lutz, AM, Rose, JE, Froeliger, B, and McClernon, FJ. "Smoking withdrawal shifts the spatiotemporal dynamics of neurocognition." Addict Biol 15.4 (October 2010): 480-490.
PMID
21040240
Source
pubmed
Published In
Addiction Biology
Volume
15
Issue
4
Publish Date
2010
Start Page
480
End Page
490
DOI
10.1111/j.1369-1600.2010.00252.x

Pulmonary delivery of nicotine pyruvate: sensory and pharmacokinetic characteristics.

The aim of this study was to evaluate pharmacokinetic and subjective responses to a prototype nicotine pyruvate (NP) aerosol generation system. In nine healthy adult daily cigarette smokers, plasma nicotine levels and subjective responses were assessed after double-blind administration of 10 inhalations of: NP (10 μg/puff, 20 μg/puff, and 30 μg/puff); Nicotrol/Nicorette nicotine vapor inhaler (NV) cartridge; and placebo (room air). Plasma nicotine concentrations increased to a significantly greater extent after inhalations of 20 μg/puff or 30 μg/puff NP (by 5.0 ± 3.4 ng/ml and 8.3 ± 3.1 ng/ml) than after placebo and NV conditions. Satisfaction ratings were higher for all NP conditions than for placebo, and harshness/irritation was lower for the NP 20 condition than for the NV control condition. Pulmonary function showed no adverse changes. These results demonstrate that NP inhalations produce rapid increases in plasma nicotine concentrations, provide satisfaction and are well tolerated. At the 20 μg/puff dose, peak nicotine concentrations were higher than with the Nicotrol/Nicorette nicotine vapor inhaler cartridge. Further trials of this promising nicotine inhalation technology are warranted to assess its safety and efficacy in smoking cessation treatment or harm reduction approaches.

Authors
Rose, JE; Turner, JE; Murugesan, T; Behm, FM; Laugesen, M
MLA Citation
Rose, JE, Turner, JE, Murugesan, T, Behm, FM, and Laugesen, M. "Pulmonary delivery of nicotine pyruvate: sensory and pharmacokinetic characteristics." Exp Clin Psychopharmacol 18.5 (October 2010): 385-394.
PMID
20939642
Source
pubmed
Published In
Experimental and Clinical Psychopharmacology
Volume
18
Issue
5
Publish Date
2010
Start Page
385
End Page
394
DOI
10.1037/a0020834

Effects of sazetidine-A, a selective alpha4beta2 nicotinic acetylcholine receptor desensitizing agent on alcohol and nicotine self-administration in selectively bred alcohol-preferring (P) rats.

RATIONALE: Manipulations of nicotinic cholinergic receptors have been shown to influence both alcohol and nicotine intake. Sazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a novel compound that potently and selectively desensitizes alpha4beta2 nicotinic receptors with only modest receptor activation. OBJECTIVES: The goal of the present study was to examine the effects of sazetidine-A on alcohol and nicotine self-administration in alcohol-preferring (P) rats. METHODS: P rats were given the choice of water or alcohol. Once stable baselines were established, the acute (0, 0.1, 0.3, 1, and 3 mg/kg, s.c.) and chronic (3 mg/kg for 10 days) effects of sazetidine-A on alcohol intake were assessed. Naltrexone (2.5 mg/kg) served as a positive control. The effect of sazetidine-A (3 mg/kg) and naltrexone (4 mg/kg) on saccharin (0.2%) preference was also assessed. In addition, the acute effects of sazetidine-A (3 mg/kg) and naltrexone (4 mg/kg) on alcohol intake after alcohol deprivation were evaluated. In another experiment, the effects of sazetidine-A (0, 1, or 3 mg/kg) on i.v. nicotine self-administration in P and NP rats were assessed. RESULTS: Sazetidine-A caused a dose-dependent reduction in alcohol intake. Chronic sazetidine-A also effectively reduced alcohol intake until the seventh day of treatment, when partial tolerance appeared to develop. In the post-deprivation study, sazetidine-A significantly reduced alcohol intake and preference. Sazetidine-A at 3 mg/kg significantly reduced nicotine self-administration in both lines. CONCLUSIONS: Sazetidine-A significantly reduced alcohol and nicotine intake in P rats that self-administer higher levels of both drugs. Sazetidine-A may hold promise for the treatment of alcohol and nicotine addiction.

Authors
Rezvani, AH; Slade, S; Wells, C; Petro, A; Lumeng, L; Li, T-K; Xiao, Y; Brown, ML; Paige, MA; McDowell, BE; Rose, JE; Kellar, KJ; Levin, ED
MLA Citation
Rezvani, AH, Slade, S, Wells, C, Petro, A, Lumeng, L, Li, T-K, Xiao, Y, Brown, ML, Paige, MA, McDowell, BE, Rose, JE, Kellar, KJ, and Levin, ED. "Effects of sazetidine-A, a selective alpha4beta2 nicotinic acetylcholine receptor desensitizing agent on alcohol and nicotine self-administration in selectively bred alcohol-preferring (P) rats." Psychopharmacology (Berl) 211.2 (August 2010): 161-174.
PMID
20535453
Source
pubmed
Published In
Psychopharmacology
Volume
211
Issue
2
Publish Date
2010
Start Page
161
End Page
174
DOI
10.1007/s00213-010-1878-8

Hippocampal and striatal gray matter volume are associated with a smoking cessation treatment outcome: results of an exploratory voxel-based morphometric analysis.

RATIONALE: Compared to nonsmokers, smokers exhibit a number of potentially important differences in regional brain structure including reduced gray matter (GM) volume and/or density in areas including frontal and cingulate cortices, thalamus, and insula. However, associations between brain structure and smoking cessation treatment outcomes have not been reported. OBJECTIVES: In the present analysis we sought to identify associations between regional GM volume--as measured by voxel-based morphometry (VBM)--and a smoking cessation treatment outcome (point prevalence abstinence at 4 weeks). METHODS: Adult smokers underwent high-resolution anatomical MRI scanning prior to an open label smoking cessation treatment trial. VBM was conducted in SPM5 using the DARTEL algorithm and relapser vs. quitter groups were compared using independent sample t tests (p < 0.001, uncorrected). Analyses controlled for potentially confounding factors including years smoked, cigarettes per day, total intracranial volume (TIV), and sex. RESULTS: Of 18 smokers, 8 achieved a 4-week point prevalence abstinence, confirmed by CO level (

Authors
Froeliger, B; Kozink, RV; Rose, JE; Behm, FM; Salley, AN; McClernon, FJ
MLA Citation
Froeliger, B, Kozink, RV, Rose, JE, Behm, FM, Salley, AN, and McClernon, FJ. "Hippocampal and striatal gray matter volume are associated with a smoking cessation treatment outcome: results of an exploratory voxel-based morphometric analysis." Psychopharmacology (Berl) 210.4 (July 2010): 577-583.
PMID
20424827
Source
pubmed
Published In
Psychopharmacology
Volume
210
Issue
4
Publish Date
2010
Start Page
577
End Page
583
DOI
10.1007/s00213-010-1862-3

Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.

Improving and targeting nicotine replacement therapy (NRT) are cost-effective strategies for reducing adverse health consequences for smokers. Treatment studies document the efficacy of precessation NRT and support important roles for level of nicotine dependence and precessation smoking reduction in successful quitting. However, prior work has not identified the optimal precessation dose or means for personalizing NRT. Genome-wide association has identified groups of genomic markers associated with successful quitting, allowing us to develop a v1.0 "quit-success" genotype score. We now report influences of v1.0 quit-success genotype score, level of dependence and precessation smoking reduction in a smoking cessation trial that examined effects of 21 versus 42 mg/24 h precessation NRT. Four hundred seventy-nine smokers were randomized to 21 or 42 mg NRT, initiated 2 wks prior to target quit dates. We monitored self-reported abstinence and end-expired air carbon monoxide (CO). Genotyping used Affymetrix arrays (Santa Clara, CA, USA). The primary outcome was 10-wk continuous smoking abstinence. NRT dose, level of nicotine dependence and genotype scores displayed significant interactive effects on successful quitting. Successful abstinence also was predicted by CO reductions during precessation NRT. These results document ways in which smoking cessation strategies can be personalized based on levels of nicotine dependence, genotype scores and CO monitoring. These assessments, taken together, can help match most smokers with optimal NRT doses and help rapidly identify some who may be better treated using other methods.

Authors
Rose, JE; Behm, FM; Drgon, T; Johnson, C; Uhl, GR
MLA Citation
Rose, JE, Behm, FM, Drgon, T, Johnson, C, and Uhl, GR. "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score." Mol Med 16.7-8 (July 2010): 247-253.
PMID
20379614
Source
pubmed
Published In
Molecular medicine (Cambridge, Mass.)
Volume
16
Issue
7-8
Publish Date
2010
Start Page
247
End Page
253
DOI
10.2119/molmed.2009.00159

Reinforcing effects of nicotine and non-nicotine components of cigarette smoke.

RATIONALE: Nicotine and non-nicotine components of cigarette smoke contribute to its reinforcing effects; however, the specific role of each component in maintaining behavior has not yet been elucidated. OBJECTIVES: To assess the reinforcing effects of nicotine and non-nicotine components of cigarette smoke by presenting a concurrent choice paradigm in which participants had access to intravenous (IV) nicotine infusions vs. saline (placebo) infusions and puffs from denicotinized ("denic") cigarettes vs. air (sham puffs). We also measured the effects on self-administration of prior satiation with each component. METHODS: Sixteen smokers participated in seven sessions: 1) a baseline smoking assessment, used to tailor the nicotine dose per infusion; 2) two sessions for training discrimination of IV nicotine vs. saline infusions and denic smoke vs. sham puffs; and 3) four sessions assessing choice behavior after different satiation conditions. RESULTS: Denic smoke was self-administered more than any other alternative, including IV nicotine. IV nicotine, however, was preferred over IV saline and sham puffs. Preference for denic smoke vs. IV nicotine was inversely correlated with subjective ratings of "comfort" associated with nicotine. Smoke satiation reduced the number of denic puffs taken during choice periods, while prior nicotine administration did not affect puffing behavior. Smoking withdrawal symptoms were alleviated both by nicotine administration and by denic smoke. CONCLUSIONS: In established smokers, non-nicotine aspects of cigarette smoking have potent reinforcing effects. While current smoking cessation pharmacotherapies primarily address the nicotine component of cigarette addiction, future cessation strategies should also be designed to target non-nicotine factors.

Authors
Rose, JE; Salley, A; Behm, FM; Bates, JE; Westman, EC
MLA Citation
Rose, JE, Salley, A, Behm, FM, Bates, JE, and Westman, EC. "Reinforcing effects of nicotine and non-nicotine components of cigarette smoke." Psychopharmacology (Berl) 210.1 (May 2010): 1-12.
PMID
20358364
Source
pubmed
Published In
Psychopharmacology
Volume
210
Issue
1
Publish Date
2010
Start Page
1
End Page
12
DOI
10.1007/s00213-010-1810-2

Nicotinic receptors in the habenula: importance for memory.

The habenula is an epithalamic structure through which descending connections pass from the telencephalon to the brainstem, putting it in a key location to provide feedback control over the brainstem monoaminergic projections ascending to the telencephalon. Habenular nuclei lesions have been shown to impair memory function. The habenular nuclei have high concentrations of nicotinic receptors. In this study we assessed the role of habenular nicotinic receptors for working memory. Adult female Sprague-Dawley rats were trained on a 16-arm maze to assess spatial working and reference memory. All rats had at least 18 sessions of training and then had bilateral chronic infusion cannulae placed into the lateral habenula nucleus. These cannulae were each connected to a slow delivery osmotic minipump that chronically infused mecamylamine 100 microg/side/day (n=9) or vehicle (aCSF) for controls (n=15) for a period of 4 weeks. Both mecamylamine-infused and control rats were acutely injected (s.c.) with nicotine (0, 0.2 or 0.4 mg/kg) in a repeated measures counterbalanced design twice at each dose during the chronic local infusion period. There was a significant (P<0.025) mecamylaminexnicotine interaction effect on memory performance. Without nicotine injection the chronic habenular mecamylamine infusion caused a significant (P<0.05) increase in total memory errors. The 0.4 mg/kg nicotine dose significantly (P<0.005) reversed the mecamylamine-induced memory impairment, returning performance back to levels seen in rats with control aCSF habenular infusions. The current study determined that nicotinic receptors in the lateral habenular nucleus are important for spatial memory function. Descending projections from the telencephalon through the habenula to brainstem nuclei using nicotinic receptors appear to be a key pathway for memory processing.

Authors
Sanders, D; Simkiss, D; Braddy, D; Baccus, S; Morton, T; Cannady, R; Weaver, N; Rose, JE; Levin, ED
MLA Citation
Sanders, D, Simkiss, D, Braddy, D, Baccus, S, Morton, T, Cannady, R, Weaver, N, Rose, JE, and Levin, ED. "Nicotinic receptors in the habenula: importance for memory." Neuroscience 166.2 (March 17, 2010): 386-390.
PMID
20034548
Source
pubmed
Published In
Neuroscience
Volume
166
Issue
2
Publish Date
2010
Start Page
386
End Page
390
DOI
10.1016/j.neuroscience.2009.12.035

Kinetics of brain nicotine accumulation in dependent and nondependent smokers assessed with PET and cigarettes containing 11C-nicotine.

Tobacco smoking is a chronic, relapsing disorder that constitutes one of the primary preventable causes of death in developed countries. Two of the popular hypotheses to explain the development and maintenance of strong nicotine dependence in cigarette smokers posit (i) a rapid brain nicotine accumulation during cigarette smoking and/or (ii) puff-associated spikes in brain nicotine concentration. To address these hypotheses, we investigated the dynamics of nicotine accumulation in the smoker's brain during actual cigarette smoking using PET with 3-s temporal resolution and (11)C-nicotine loaded into cigarettes. The results of the study, performed in 13 dependent smokers (DS) and 10 nondependent smokers (NDS), suggest that puff-associated spikes in the brain nicotine concentration do not occur during habitual cigarette smoking. Despite the presence of a puff-associated oscillation in the rate of nicotine accumulation, brain nicotine concentration gradually increases during cigarette smoking. The results further suggest that DS have a slower process of brain nicotine accumulation than NDS because they have slower nicotine washout from the lungs and that DS have a tendency to compensate for their slower rate of brain nicotine accumulation compared with NDS by inhaling a larger volume of smoke. For these reasons, smokers' dependence on cigarette smoking, or the resistance of NDS to becoming dependent, cannot be explained solely by a faster brain nicotine accumulation.

Authors
Rose, JE; Mukhin, AG; Lokitz, SJ; Turkington, TG; Herskovic, J; Behm, FM; Garg, S; Garg, PK
MLA Citation
Rose, JE, Mukhin, AG, Lokitz, SJ, Turkington, TG, Herskovic, J, Behm, FM, Garg, S, and Garg, PK. "Kinetics of brain nicotine accumulation in dependent and nondependent smokers assessed with PET and cigarettes containing 11C-nicotine." Proc Natl Acad Sci U S A 107.11 (March 16, 2010): 5190-5195.
PMID
20212132
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
107
Issue
11
Publish Date
2010
Start Page
5190
End Page
5195
DOI
10.1073/pnas.0909184107

Sazetidine-A, a selective alpha4beta2 nicotinic receptor desensitizing agent and partial agonist, reduces nicotine self-administration in rats.

Adequate treatment of tobacco addiction remains problematic. Part of the problem with treatment is a poor understanding of the pharmacologic aspects of nicotine contributing to addiction. In addition to activating nicotinic acetylcholine receptors, nicotine also desensitizes them. It is currently not known how much of each of nicotine's actions contribute to its particular behavioral effects. Sazetidine-A (saz-A) is a novel nicotinic receptor-desensitizing agent and partial agonist with high selectivity for alpha4beta2 receptors. The current experiments were conducted to determine whether saz-A would reduce nicotine self-administration in rats and to characterize its ancillary effects. Adult male Sprague-Dawley rats were allowed to self-administer nicotine. After initial food pellet training followed by 10 sessions of nicotine self-administration training, the rats were administered saz-A (0.1-3 mg/kg s.c.) or the saline vehicle in a repeated-measures counterbalanced design. Saz-A at the 3 mg/kg dose significantly decreased nicotine self-administration relative to performance of the same rats after saline injections. In a second study, long-term administration of this dose of sazetidine-A over the course of 10 sessions significantly reduced nicotine self-administration with no apparent diminution of effect. Saz-A in this dose range had only modest effects on locomotor activity, without any overall decrease in activity over a 1-h-long session. Saz-A significantly reduced food self-administration, but this effect was smaller than its effect on nicotine self-administration. Saz-A, which is a selective alpha4beta2-desensitizing agent and partial agonist, effectively reduces nicotine self-administration. This type of treatment holds promise for a new therapy to aid smoking cessation.

Authors
Levin, ED; Rezvani, AH; Xiao, Y; Slade, S; Cauley, M; Wells, C; Hampton, D; Petro, A; Rose, JE; Brown, ML; Paige, MA; McDowell, BE; Kellar, KJ
MLA Citation
Levin, ED, Rezvani, AH, Xiao, Y, Slade, S, Cauley, M, Wells, C, Hampton, D, Petro, A, Rose, JE, Brown, ML, Paige, MA, McDowell, BE, and Kellar, KJ. "Sazetidine-A, a selective alpha4beta2 nicotinic receptor desensitizing agent and partial agonist, reduces nicotine self-administration in rats." J Pharmacol Exp Ther 332.3 (March 2010): 933-939.
PMID
20007754
Source
pubmed
Published In
The Journal of pharmacology and experimental therapeutics
Volume
332
Issue
3
Publish Date
2010
Start Page
933
End Page
939
DOI
10.1124/jpet.109.162073

IV nicotine self-administration in rats using the consummatory operant licking response

Nicotine self-administered by tobacco smoking or chewing is very addictive in humans. Rat models have been developed in which nicotine is self-administered IV by the rats pressing a lever. However the reinforcing value of nicotine is much less in these models than the addictiveness of human tobacco use would indicate. The IV nicotine self-administration operant lever press model does not fully capture important aspects of tobacco use in humans. Conditioned oral consumption actions of smoking or chewing tobacco may play important roles in tobacco addiction. Neural circuitry underlying essential food consummatory responses may facilitate consummatory aspects of tobacco intake. To capture this motor consummatory aspect of tobacco addiction in the rat model of nicotine self-administration, we have developed a method of using a licking response instead of a lever press to self-administer IV nicotine. Sprague-Dawley rats were trained to lick one of two waterspouts for IV nicotine (0.03. mg/kg/infusion). With the licking response rats self-administered stable nicotine levels throughout 24 sessions (45. min each) of testing. The number of total licks/session significantly increased in a linear fashion over that period. The number of licks/infusion was substantial, rising steadily with training to an average of over 100 licks/infusion. Including the consummatory motor act with nicotine self-administration could help better model the compulsive aspects of tobacco addiction in humans. © 2010 Elsevier Inc.

Authors
Levin, ED; Hampton, D; Rose, JE
MLA Citation
Levin, ED, Hampton, D, and Rose, JE. "IV nicotine self-administration in rats using the consummatory operant licking response." Physiology and Behavior 101.5 (2010): 755-758.
PMID
20804779
Source
scival
Published In
Physiology & Behavior
Volume
101
Issue
5
Publish Date
2010
Start Page
755
End Page
758
DOI
10.1016/j.physbeh.2010.08.016

Genome-wide association for smoking cessation success in a trial of precessation nicotine replacement

Abilities to successfully quit smoking display substantial evidence for heritability in classic and molecular genetic studies. Genomewide association (GWA) studies have demonstrated single-nucleotide polymorphisms (SNPs) and haplotypes that distinguish successful quitters from individuals who were unable to quit smoking in clinical trial participants and in community samples. Many of the subjects in these clinical trial samples were aided by nicotine replacement therapy (NRT). We now report novel GWA results from participants in a clinical trial that sought dose/response relationships for "precessation" NRT. In this trial, 369 European-American smokers were randomized to 21 or 42 mg NRT, initiated 2 wks before target quit dates. Ten-week continuous smoking abstinence was assessed on the basis of self-reports and carbon monoxide levels. SNP genotyping used Affymetrix 6.0 arrays. GWA results for smoking cessation success provided no P value that reached "genome-wide" significance. Compared with chance, these results do identify (a) more clustering of nominally positive results within small genomic regions, (b) more overlap between these genomic regions and those identified in six prior successful smoking cessation GWA studies and (c) sets of genes that fall into gene ontology categories that appear to be biologically relevant. The 1,000 SNPs with the strongest associations form a plausible Bayesian network; no such network is formed by randomly selected sets of SNPs. The data provide independent support, based on individual genotyping, for many loci previously nominated on the basis of data from genotyping in pooled DNA samples. These results provide further support for the idea that aid for smoking cessation may be personalized on the basis of genetic predictors of outcome. © 2010 The Feinstein Institute for Medical Research.

Authors
Uhl, GR; Drgon, T; Johnson, C; Ramoni, MF; Behm, FM; Rose, JE
MLA Citation
Uhl, GR, Drgon, T, Johnson, C, Ramoni, MF, Behm, FM, and Rose, JE. "Genome-wide association for smoking cessation success in a trial of precessation nicotine replacement." Molecular Medicine 16.11-12 (2010): 513-526.
PMID
20811658
Source
scival
Published In
Molecular medicine (Cambridge, Mass.)
Volume
16
Issue
11-12
Publish Date
2010
Start Page
513
End Page
526
DOI
10.2119/molmed.2010.00052

Genome-wide meta-analyses identify multiple loci associated with smoking behavior

Consistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], Β = 1.03, standard error (s.e.) = 0.053, P = 2.8 × 10 73). Two 10q25 SNPs (rs1329650[G], Β = 0.367, s.e. = 0.059, P = 5.7 × 10 10; and rs1028936[A], Β = 0.446, s.e. = 0.074, P = 1.3 × 10 9) and one 9q13 SNP in EGLN2 (rs3733829[G], Β = 0.333, s.e. = 0.058, P = 1.0 × 10 8) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 × 10 8). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 × 10 8) was significantly associated with smoking cessation. © 2010 Nature America, Inc. All rights reserved.

Authors
Furberg, H; Kim, Y; Dackor, J; Boerwinkle, E; Franceschini, N; Ardissino, D; Bernardinelli, L; Mannucci, PM; Mauri, F; Merlini, PA; Absher, D; Assimes, TL; Fortmann, SP; Iribarren, C; Knowles, JW; Quertermous, T; Ferrucci, L; Tanaka, T; Bis, JC; Furberg, CD; Haritunians, T; McKnight, B; Psaty, BM; Taylor, KD; Thacker, EL; Almgren, P; Groop, L; Ladenvall, C; Boehnke, M; Jackson, AU; Mohlke, KL; Stringham, HM; Tuomilehto, J; Benjamin, EJ; Hwang, S-J; Levy, D; Preis, SR; Vasan, RS; Duan, J et al.
MLA Citation
Furberg, H, Kim, Y, Dackor, J, Boerwinkle, E, Franceschini, N, Ardissino, D, Bernardinelli, L, Mannucci, PM, Mauri, F, Merlini, PA, Absher, D, Assimes, TL, Fortmann, SP, Iribarren, C, Knowles, JW, Quertermous, T, Ferrucci, L, Tanaka, T, Bis, JC, Furberg, CD, Haritunians, T, McKnight, B, Psaty, BM, Taylor, KD, Thacker, EL, Almgren, P, Groop, L, Ladenvall, C, Boehnke, M, Jackson, AU, Mohlke, KL, Stringham, HM, Tuomilehto, J, Benjamin, EJ, Hwang, S-J, Levy, D, Preis, SR, Vasan, RS, and Duan, J et al. "Genome-wide meta-analyses identify multiple loci associated with smoking behavior." Nature Genetics 42.5 (2010): 441-447.
PMID
20418890
Source
scival
Published In
Nature Genetics
Volume
42
Issue
5
Publish Date
2010
Start Page
441
End Page
447
DOI
10.1038/ng.571

Co-expression of nAChRs and molecules of the bitter taste transduction pathway by epithelial cells of intrapulmonary airways

Aims: The ability to sense the bitter taste of nicotine is an important component of addiction to, and withdrawal from, cigarette smoking α-Gustducin and phospholipase C-β2 (PLC-β2), molecules involved in the taste transduction pathway, have been identified in airway epithelial solitary chemosensory cells (SCCs). Airway epithelial cells also express multiple nicotinic acetylcholine receptors (nAChRs). However, the relationship between nAChRs and molecules of taste transduction in response to nicotine is not known. This study was designed to determine whether nAChRs and the taste transduction molecules α-gustducin, PLC-β2 and bitter taste receptors (T2R38) reside at sites of the intrapulmonary airways where interaction with the nicotine components of cigarette smoke is likely. Main methods: We used the reverse transcription-polymerase chain reaction (RT-PCR) to detect α-gustducin, PLC-β2 and T2R38 mRNA and immunohistochemistry to localize expression of these proteins by nAChR expressing cells of the airway. Key findings: RT-PCR demonstrated the presence of mRNA for α-gustducin, PLC-β2 and T2R38. Immunohistochemistry showed the expression of α-gustducin, PLC-β2 and T2R38 by subsets of epithelial cells at all levels of the intrapulmonary airways including bronchi, terminal and respiratory bronchioles. Double labeling demonstrated the co-expression of α-gustducin with α3, α4, α5, α7 and β2, as well as, PLC-β2 and T2R38 with α4, α5 and β2 nAChR subunits. Significance: These findings provide morphological evidence for the presence of molecules of the bitter taste transduction pathway in nAChR expressing SCCs of the intrapulmonary airways. These SCCs may, thus, constitute a peripheral component of the bitter taste signal transduction pathway for nicotine. © 2010 Elsevier Inc.

Authors
Dehkordi, O; Rose, JE; Balan, KV; Millis, RM; Bhatti, B; Jayam-Trouth, A
MLA Citation
Dehkordi, O, Rose, JE, Balan, KV, Millis, RM, Bhatti, B, and Jayam-Trouth, A. "Co-expression of nAChRs and molecules of the bitter taste transduction pathway by epithelial cells of intrapulmonary airways." Life Sciences 86.7-8 (2010): 281-288.
PMID
20060845
Source
scival
Published In
Life Sciences
Volume
86
Issue
7-8
Publish Date
2010
Start Page
281
End Page
288
DOI
10.1016/j.lfs.2009.12.016

Precessation treatment with nicotine patch significantly increases abstinence rates relative to conventional treatment.

INTRODUCTION: Previous studies have reported that smoking abstinence rates are increased when nicotine skin patch treatment is initiated prior to the target quit smoking date, as compared with conventional treatment beginning on the quit date. We hypothesized that smoking in the presence of continuous levels of nicotine would attenuate the reinforcing effects of cigarette smoking and lead to a decline in dependence on inhaled nicotine, thus facilitating cessation. METHODS: This study involved four groups of smokers (n = 100 per group) who received either nicotine patch (21 mg/24 hr) or placebo patch treatment for 2 weeks before the quit smoking date, and during this period, smoked their usual brands of cigarettes or switched to low-tar and nicotine cigarettes: a 2 (nicotine patch) x 2 (cigarette type) factorial design. From the quit date on, all groups received standard nicotine patch treatment, consisting of 6 weeks of 21 mg/24 hr, 2 weeks of 14 mg/24 hr, and 2 weeks of 7 mg/24 hr. Abstinence was defined as self-report of no smoking from the quit date on, confirmed by expired-air carbon monoxide. RESULTS: Continuous abstinence rates were approximately doubled by precessation nicotine patch treatment. The treatment mainly benefited smokers with lower levels of dependence, based on Fagerström Test for Nicotine Dependence score. All treatments were well tolerated. DISCUSSION: In view of these findings and similar results from previous studies, current labeling of the nicotine patch, which recommends using nicotine replacement therapy only after the quit date, should be reexamined.

Authors
Rose, JE; Herskovic, JE; Behm, FM; Westman, EC
MLA Citation
Rose, JE, Herskovic, JE, Behm, FM, and Westman, EC. "Precessation treatment with nicotine patch significantly increases abstinence rates relative to conventional treatment." Nicotine Tob Res 11.9 (September 2009): 1067-1075.
PMID
19567826
Source
pubmed
Published In
Nicotine and Tobacco Research (OUP)
Volume
11
Issue
9
Publish Date
2009
Start Page
1067
End Page
1075
DOI
10.1093/ntr/ntp103

24-h smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum.

RATIONALE: Exposure to smoking-related cues can trigger relapse in smokers attempting to maintain abstinence. OBJECTIVES: In the present study, we evaluated the effect of 24-h smoking abstinence on brain responses to smoking-related cues using functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: Eighteen adult smokers underwent fMRI scanning following smoking as usual (satiated condition) and following 24-h abstinence (abstinent condition). During scanning, they viewed blocks of photographic smoking and control cues. RESULTS: Following abstinence, greater activation was found in response to smoking cues compared to control cues in parietal (BA 7/31), frontal (BA 8/9), occipital (BA 19), and central (BA 4) cortical regions and in dorsal striatum (putamen) and thalamus. In contrast, no smoking cue greater than control cue activations were observed following smoking as usual. Direct comparisons between conditions (satiated vs. abstinent) showed greater brain reactivity in response to smoking cues following abstinence. In addition, positive correlations between pre-scan craving in the abstinent condition and smoking cue activation were observed in right dorsomedial prefrontal cortex (dmPFC) including superior frontal gyrus (BA 6/10), anterior cingulate gyrus (BA 32), and supplementary motor area (BA 6). CONCLUSIONS: The present findings indicate that smoking abstinence significantly potentiates neural responses to smoking-related cues in brain regions subserving visual sensory processing, attention, and action planning. Moreover, greater abstinence-induced craving was significantly correlated with increased smoking cue activation in dmPFC areas involved in action planning and decision making. These findings suggest that drug abstinence can increase the salience of conditioned cues, which is consistent with incentive-motivation models of addiction.

Authors
McClernon, FJ; Kozink, RV; Lutz, AM; Rose, JE
MLA Citation
McClernon, FJ, Kozink, RV, Lutz, AM, and Rose, JE. "24-h smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum." Psychopharmacology (Berl) 204.1 (May 2009): 25-35.
PMID
19107465
Source
pubmed
Published In
Psychopharmacology
Volume
204
Issue
1
Publish Date
2009
Start Page
25
End Page
35
DOI
10.1007/s00213-008-1436-9

Brain nicotinic acetylcholine receptor occupancy: effect of smoking a denicotinized cigarette.

Our group recently reported that smoking a regular cigarette (1.2-1.4 mg nicotine) resulted in 88% occupancy of brain alpha4beta2* nicotinic acetylcholine receptors (nAChRs). However, this study did not determine whether nicotine inhalation or the many other pharmacological and behavioural factors that occur during smoking resulted in this receptor occupancy. If nicotine is solely responsible for alpha4beta2* nAChR occupancy from smoking, then (as estimated from our previous data) smoking a denicotinized (0.05 mg nicotine) or a low-nicotine (0.6 mg nicotine) cigarette (commonly used for research and clinical purposes) would result in substantial 23% and 78% alpha4beta2* nAChR occupancies, respectively, and a plasma nicotine concentration of 0.87 ng/ml would result in 50% alpha4beta2* nAChR occupancy (EC50). Twenty-four positron emission tomography sessions were performed on tobacco-dependent smokers, using 2-[F-18]fluoro-A-85380 (2-FA), a radiotracer that binds to alpha4beta2* nAChRs. 2-FA displacement was determined from before to 3.1 hours after either: no smoking, smoking a denicotinized cigarette, or smoking a low-nicotine cigarette. Analysis of this PET data revealed that smoking a denicotinized and a low-nicotine cigarette resulted in 26% and 79% alpha4beta2* nAChR occupancies, respectively, across three regions of interest. The EC50 determined from this dataset was 0.75 ng/ml. Given the consistency of findings between our previous study with regular cigarettes and the present study, nicotine inhalation during smoking appears to be solely responsible for alpha4beta2* nAChR occupancy, with other factors (if present at all) having either short-lived or very minor effects. Furthermore, smoking a denicotinized cigarette resulted in substantial nAChR occupancy.

Authors
Brody, AL; Mandelkern, MA; Costello, MR; Abrams, AL; Scheibal, D; Farahi, J; London, ED; Olmstead, RE; Rose, JE; Mukhin, AG
MLA Citation
Brody, AL, Mandelkern, MA, Costello, MR, Abrams, AL, Scheibal, D, Farahi, J, London, ED, Olmstead, RE, Rose, JE, and Mukhin, AG. "Brain nicotinic acetylcholine receptor occupancy: effect of smoking a denicotinized cigarette." Int J Neuropsychopharmacol 12.3 (April 2009): 305-316.
PMID
18706128
Source
pubmed
Published In
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)
Volume
12
Issue
3
Publish Date
2009
Start Page
305
End Page
316
DOI
10.1017/S146114570800922X

Nicotinic alpha7- or beta2-containing receptor knockout: effects on radial-arm maze learning and long-term nicotine consumption in mice.

Classically, it has been thought that high-affinity nicotinic receptors-containing beta2 subunits are the most important receptor subtypes for nicotinic involvement in cognitive function and nicotine self-administration, while low affinity alpha7-containing nicotinic receptors have not been thought to be important. In the current study, we found that knockout of either beta2 or alpha7 subunits caused significant deficits in spatial discrimination in mice. The character of the impairment in the two knockouts was different. The beta2 knockout preferentially impaired cognition in males while the alpha7 caused impairment regardless of sex. Both beta2- and alpha7-containing nicotinic receptors also are important for nicotine self-administration, also in different ways. Most animal model studies of nicotine self-administration are relatively short-term whereas the problem of tobacco addiction is considerably longer-term. To better model the impact of nicotinic receptor subtypes on nicotine self-administration over the long-term, we studied the impact of genetic knockout of low affinity alpha7 receptors vs. high-affinity beta2-containing nicotinic receptors. Mice with knockouts of either of these receptors and their wildtype counter parts were given free access to a choice of nicotine-containing and nicotine-free solution in their home cages on a continuous basis over a period of 5 months. During the first few weeks, the beta2-containing nicotinic receptor knockout mice showed a significant decrease in nicotine consumption relative to wildtype mice, whereas the alpha7 knockout mice did not significantly differ from wildtype controls at the beginning of their access to nicotine. Interestingly, in the longer-term after the first few weeks of nicotine access, the beta2 knockout mice returned to wildtype mouse levels of nicotine consumption, whereas the alpha7 knockout mice developed an emergent decrease in nicotine consumption. The alpha7 receptor knockout-induced decrease in nicotine consumption persisted for the 5-month period of the study. Both alpha7- and beta2-containing nicotinic receptors play critical roles in cognitive function and nicotine self-administration. Regarding cognitive function, beta2-containing receptors are important for maintaining normal sex differences in spatial learning and memory, whereas alpha7 receptors are important for cognitive function regardless of sex. Regarding nicotine self-administration high-affinity beta2-containing nicotinic receptors are important for consumption during the initial phase of nicotine access, but it is the alpha7 nicotinic receptors that are important for the longer-term regulation of nicotine consumption.

Authors
Levin, ED; Petro, A; Rezvani, AH; Pollard, N; Christopher, NC; Strauss, M; Avery, J; Nicholson, J; Rose, JE
MLA Citation
Levin, ED, Petro, A, Rezvani, AH, Pollard, N, Christopher, NC, Strauss, M, Avery, J, Nicholson, J, and Rose, JE. "Nicotinic alpha7- or beta2-containing receptor knockout: effects on radial-arm maze learning and long-term nicotine consumption in mice." Behav Brain Res 196.2 (January 23, 2009): 207-213.
PMID
18831991
Source
pubmed
Published In
Behavioural Brain Research
Volume
196
Issue
2
Publish Date
2009
Start Page
207
End Page
213
DOI
10.1016/j.bbr.2008.08.048

Genome-wide association for smoking cessation success: Participants in a trial with adjunctive denicotinized cigarettes

The ability to quit smoking successfully displays substantial heritability in classical and molecular genetic studies. Twin studies suggest that some of the genetics for the ability to quit overlap with genetic components of nicotine dependence, but many do not. Genome-wide association (GWA) studies have demonstrated haplotypes that distinguish successful quitters from individuals who were not able to quit smoking in: i) clinical trials that employed nicotine replacement; ii) clinical trials that employed bupropion; and iii) community quitter samples.We now report novel GWA results from participants in a clinical trial that document the efficacy of adjunctive use of denicotinized cigarettes. These results buttress data from our prior GWA studies of smoking cessation. They suggest that ability to change smoking behavior using denicotinized cigarettes shares substantial underlying genetics with the ability to change this behavior in community settings or in response to treatments with nicotine replacement or bupropion. © 2009 The Feinstein Institute for Medical Research.

Authors
Drgon, T; Johnson, C; Walther, D; Albino, AP; Rose, JE; Uhl, GR
MLA Citation
Drgon, T, Johnson, C, Walther, D, Albino, AP, Rose, JE, and Uhl, GR. "Genome-wide association for smoking cessation success: Participants in a trial with adjunctive denicotinized cigarettes." Molecular Medicine 15.7-8 (2009): 268-274.
PMID
19593411
Source
scival
Published In
Molecular medicine (Cambridge, Mass.)
Volume
15
Issue
7-8
Publish Date
2009
Start Page
268
End Page
274
DOI
10.2119/molmed.2009.00040

Neuroanatomical relationships of substance P-immunoreactive intrapulmonary C-fibers and nicotinic cholinergic receptors

Previous studies have suggested that sensory mechanisms may be important components of addiction to, and withdrawal from, cigarette smoking. The sensory and respiratory responses to nicotine are mediated, in part, by bronchopulmonary C-fiber afferents. Nicotine has a direct stimulatory effect on pulmonary sensory neurons, and nicotinic cholinergic receptors (nAChRs) composed of various combinations of α and β subunits are known to be present in pulmonary ganglia. At the subcellular level, however, little is known about expression of nAChRs on sensory fibers in the intrapulmonary airways. The present study was therefore designed to evaluate the expression of nAChRs on a subset of intrapulmonary sensory nerve endings known to exhibit immunoreactivity for substance P (SP). The presence of nAChR subunits was first confirmed at the mRNA and protein levels in rat lung tissues by using RT-PCR and Western blot techniques. Then, double labeling of SP-immunoreactive (-IR) C-fibers and different nAChR subunits was performed. α2, α3, α4, α5, α7, and β2 subunits were detected at all levels of the intrapulmonary airways; including bronchi, terminal and respiratory bronchioles, alveolar walls, and alveolar macrophages. None of the nAChR subunits studied was expressed by the SP-IR C-fibers. However, SP-expressing C-fibers were observed in close proximity to and intermingling with nAChR-expressing airway epithelial cells. The close proximity of C-fibers to nAChR-expressing airway epithelial cells suggests that a component of nicotinic stimulation of SP-IR C-fiber afferents may be mediated by endogenous chemical substances released by nAChR-expressing epithelial cells. © 2008 Wiley-Liss, Inc.

Authors
Dehkordi, O; Rose, JA; Balan, KV; Kc, P; Millis, RM; Jayam-Trouth, A
MLA Citation
Dehkordi, O, Rose, JA, Balan, KV, Kc, P, Millis, RM, and Jayam-Trouth, A. "Neuroanatomical relationships of substance P-immunoreactive intrapulmonary C-fibers and nicotinic cholinergic receptors." Journal of Neuroscience Research 87.7 (2009): 1670-1678.
PMID
19115400
Source
scival
Published In
Journal of Neuroscience Research
Volume
87
Issue
7
Publish Date
2009
Start Page
1670
End Page
1678
DOI
10.1002/jnr.21967

New findings on nicotine addiction and treatment.

Authors
Rose, JE
MLA Citation
Rose, JE. "New findings on nicotine addiction and treatment." Nebr Symp Motiv 55 (2009): 131-141. (Review)
PMID
19013942
Source
pubmed
Published In
Nebraska Symposium on Motivation
Volume
55
Publish Date
2009
Start Page
131
End Page
141

Nicotine abstinence genotyping: Assessing the impact on smoking cessation clinical trials

Twin studies document substantial heritability for successful abstinence from smoking. A genome-wide association study has identified markers whose allele frequencies differ with nominal P < 0.005 in nicotine-dependent clinical trial participants who were successful vs unsuccessful in abstaining from smoking; many of these results are also supported by data from two additional samples. More study is required to precisely determine the variance in quitting success that can be accounted for by the single-nucleotide polymorphisms that are currently identified and to precisely classify individuals who may display varying degrees of genetic vs environmental effects into quitters or nonquitters. However, the data at hand do allow us to model the effects of genotypic stratification in smoking cessation trials. We identify relationships between the costs of identifying and genotyping prospective trial participants vs the costs of performing the clinical trials. We quantitate the increasing savings that result from genetically stratified designs as recruiting/genotyping costs go down and trial costs increase. This model helps to define the circumstances in which genetically stratified designs may enhance power and reduce costs for smoking cessation clinical trials.

Authors
Uhl, GR; Drgon, T; Johnson, C; Rose, JE
MLA Citation
Uhl, GR, Drgon, T, Johnson, C, and Rose, JE. "Nicotine abstinence genotyping: Assessing the impact on smoking cessation clinical trials." Pharmacogenomics Journal 9.2 (2009): 111-115.
PMID
18781146
Source
scival
Published In
The Pharmacogenomics Journal
Volume
9
Issue
2
Publish Date
2009
Start Page
111
End Page
115
DOI
10.1038/tpj.2008.10

Ketanserin, a 5-HT2 receptor antagonist, decreases nicotine self-administration in rats.

Nicotine intake constitutes a principal mechanism for tobacco addiction. In addition to primary effects on nicotinic acetylcholine receptors, nicotine has cascading effects, which may also underlie its neurobehavioral actions. Nicotine induces serotonin (5-HT) release, which has not classically been thought to be involved in tobacco addiction as dopamine has. However, addiction can be characterized more as a disorder of compulsion than a disorder of enjoyment. 5-HT mechanisms play key roles in compulsive disorders. Nicotine-induced 5-HT release may be a key to tobacco addiction. Ketanserin, a 5-HT2a and 5-HT2c receptor antagonist, significantly attenuates nicotine effects on attention and memory. These studies were conducted to determine if ketanserin would reduce nicotine self-administration in rats. Male Sprague-Dawley rats (N=12) were given initial food pellet training and then 10 sessions of nicotine self-administration training (0.03 mg/kg/infusion, i.v.). Then the rats were administered ketanserin (1 or 2 mg/kg, s.c.) or the saline vehicle. Ketanserin (2 mg/kg) significantly decreased nicotine self-administration. This did not seem to be due to sedative or amnestic effects of ketanserin. In a second study, the effects of repeated administration of 2 mg/kg ketanserin (N=11) vs. saline injections (N=10) were examined. In the initial phase, the acute effectiveness of ketanserin in significantly reducing nicotine self-administration was replicated. The effect became attenuated during the following several sessions, but the significant effect became re-established during the final phases of this two-week study. 5-HT mechanisms play critical roles in the maintenance of nicotine self-administration. Better understanding of those roles may help lead to new 5-HT-based treatments for tobacco addiction.

Authors
Levin, ED; Slade, S; Johnson, M; Petro, A; Horton, K; Williams, P; Rezvani, AH; Rose, JE
MLA Citation
Levin, ED, Slade, S, Johnson, M, Petro, A, Horton, K, Williams, P, Rezvani, AH, and Rose, JE. "Ketanserin, a 5-HT2 receptor antagonist, decreases nicotine self-administration in rats." Eur J Pharmacol 600.1-3 (December 14, 2008): 93-97.
PMID
18950618
Source
pubmed
Published In
European Journal of Pharmacology
Volume
600
Issue
1-3
Publish Date
2008
Start Page
93
End Page
97
DOI
10.1016/j.ejphar.2008.10.016

Disrupting nicotine reinforcement: from cigarette to brain.

Cigarette smoking is a tenacious addiction that is maintained to a significant extent by the reinforcing effects of nicotine. An emerging theme in smoking cessation treatment is the development of methods for interfering with these reinforcing effects. By attenuating nicotine reinforcement, treatments may enhance a smoker's chances of successfully remaining abstinent. Several treatment approaches will be described, including the use of denicotinized cigarettes, nicotine vaccines, nicotinic receptor agonists and antagonists, and modulators of brain reinforcement processes. These techniques highlight the numerous sites along the path between the cigarette and the brain that can be targeted for intervention. In addition to unimodal therapies, treatment combinations will be discussed that might more effectively block cigarette reward and thereby further enhance smoking abstinence.

Authors
Rose, JE
MLA Citation
Rose, JE. "Disrupting nicotine reinforcement: from cigarette to brain." Ann N Y Acad Sci 1141 (October 2008): 233-256. (Review)
PMID
18991961
Source
pubmed
Published In
Annals of the New York Academy of Sciences
Volume
1141
Publish Date
2008
Start Page
233
End Page
256
DOI
10.1196/annals.1441.019

Individual differences in nicotine dependence, withdrawal symptoms, and sex predict transient fMRI-BOLD responses to smoking cues.

Exposure to smoking cues increases craving for cigarettes and can precipitate relapse. Whereas brain imaging studies have identified a distinct network of brain regions subserving the processing of smoking cues, little is known about the influence of individual difference factors and withdrawal symptoms on brain cue reactivity. Multiple regression analysis was used to evaluate relations between individual difference factors and withdrawal symptoms and event-related blood oxygen level-dependent responses to visual smoking cues in a sample of 30 smokers. Predictors were self-report nicotine dependence (Fagerström test of nicotine dependence, FTND), prescan withdrawal symptoms (craving and negative affect), and sex. The unique variance of each predictor was examined after controlling for each of the others. Positive associations were observed between FTND and reactivity to cues in right anterior cingulate and orbitofrontal cortex (OFC) whereas negative associations were observed between prescan craving and reactivity in ventral striatum. Higher negative affect or being male was associated with greater reactivity in left hippocampus and left OFC. Women exhibited greater cue reactivity than men in regions including the cuneus and left superior temporal gyrus. Individual difference factors and withdrawal symptoms were uniquely associated with brain reactivity to smoking cues in regions subserving reward, affect, attention, motivation, and memory. These findings provide further evidence that reactivity to conditioned drug cues is multiply determined and suggest that smoking cessation treatments designed to reduce cue reactivity focus on each of these variables.

Authors
McClernon, FJ; Kozink, RV; Rose, JE
MLA Citation
McClernon, FJ, Kozink, RV, and Rose, JE. "Individual differences in nicotine dependence, withdrawal symptoms, and sex predict transient fMRI-BOLD responses to smoking cues." Neuropsychopharmacology 33.9 (August 2008): 2148-2157.
PMID
17987060
Source
pubmed
Published In
Neuropsychopharmacology (Nature)
Volume
33
Issue
9
Publish Date
2008
Start Page
2148
End Page
2157
DOI
10.1038/sj.npp.1301618

Effects of smoking abstinence on adult smokers with and without attention deficit hyperactivity disorder: results of a preliminary study.

RATIONALE: Individuals with attention deficit hyperactivity disorder (ADHD) smoke at higher rates than the general population; however, little is known about the mechanisms underlying this comorbidity. OBJECTIVE: This study evaluated the effects of overnight abstinence on withdrawal symptoms and cognitive performance in adult smokers with and without ADHD. MATERIALS AND METHODS: Individuals smoking > or = 15 cigarettes per day were recruited from the community and underwent an evaluation to establish a diagnosis of ADHD (n = 12) or not (n = 14). Withdrawal symptoms, mood, craving, cognitive performance, and smoking cue reactivity were measured during two laboratory sessions-in a 'Satiated' condition participants smoked up to and during the session while in an 'Abstinent' condition, participants were required to be smoking abstinent overnight and remain abstinent during the session. RESULTS: The effects of abstinence on ADHD and non-ADHD smokers did not differ for withdrawal symptom severity, mood, craving or cue reactivity. Significant Group x Condition interactions were observed for measures of attention and response inhibition on the Conners' CPT. For reaction time (RT) variability and errors of commission, the ADHD group exhibited greater decrements in performance after overnight abstinence compared to the non-ADHD group. The effects of abstinence on other cognitive measures (e.g., rapid visual information processing task, cued Go/No-Go task) did not differ between the two groups. CONCLUSION: This preliminary study is the first to systematically evaluate the effects of acute smoking abstinence in adult smokers diagnosed with ADHD. Individuals with the disorder may smoke at higher rates due to greater worsening of attention and response inhibition after abstinence.

Authors
McClernon, FJ; Kollins, SH; Lutz, AM; Fitzgerald, DP; Murray, DW; Redman, C; Rose, JE
MLA Citation
McClernon, FJ, Kollins, SH, Lutz, AM, Fitzgerald, DP, Murray, DW, Redman, C, and Rose, JE. "Effects of smoking abstinence on adult smokers with and without attention deficit hyperactivity disorder: results of a preliminary study." Psychopharmacology (Berl) 197.1 (March 2008): 95-105.
PMID
18038223
Source
pubmed
Published In
Psychopharmacology
Volume
197
Issue
1
Publish Date
2008
Start Page
95
End Page
105
DOI
10.1007/s00213-007-1009-3

Pre-cessation varenicline treatment vs post-cessation NRT: An uneven playing field

Authors
Rose, JE
MLA Citation
Rose, JE. "Pre-cessation varenicline treatment vs post-cessation NRT: An uneven playing field." Thorax 63.8 (2008): 751-752.
PMID
18663077
Source
scival
Published In
Thorax
Volume
63
Issue
8
Publish Date
2008
Start Page
751
End Page
752

A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation

A randomized double-blind, active controlled, parallel group, multi-center phase II clinical trial was conducted to evaluate the efficacy of reduced-nicotine cigarettes as a novel smoking cessation treatment (under Investigational Device Exemption 69,185). The concept for a reduced-nicotine cigarette designed to progressively wean smokers from the smoking habit is based on research demonstrating that successful smoking cessation is not only dependent on withdrawal of nicotine, but also on weaning from the habitual sensory and behavioral reinforcement of smoking. Treatment consisted of Quest brand of cigarettes (Quest 1, 2, and 3), which respectively deliver 0.59 ± 0.06, 0.3 ± 0.05, and less than 0.05 mg nicotine, either alone or in combination with nicotine replacement therapy (NRT). The primary endpoint was 4 weeks of continuous abstinence (Weeks 7 - 10), with additional follow-up at 3 and 6 months. Adult men and women smokers (N = 346), motivated to quit, were randomized to one of three treatment groups: Quest plus NRT (NRT pretreatment 2 weeks before, and NRT after the quit date), Quest plus placebo patch, or active control plus NRT (conventional cigarette, followed by NRT after quit date). Results showed that Quest plus NRT was more effective than active control plus NRT in achieving 4 weeks of continuous abstinence (32.8% vs. 21.9%). Quest plus placebo patch yielded an abstinence rate similar to that of the active control plus NRT (16.4% vs. 21.9%). No serious adverse events were attributable to the investigational product. Quest plus NRT offers promise as a new smoking cessation treatment.

Authors
Becker, KM; Rose, JE; Albino, AP
MLA Citation
Becker, KM, Rose, JE, and Albino, AP. "A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation." Nicotine and Tobacco Research 10.7 (2008): 1139-1148.
PMID
18629723
Source
scival
Published In
Nicotine and Tobacco Research (OUP)
Volume
10
Issue
7
Publish Date
2008
Start Page
1139
End Page
1148
DOI
10.1080/14622200802123294

Molecular genetics of successful smoking cessation: Convergent genome-wide association study results

Context: Smoking remains a major public health problem. Twin studies indicate that the ability to quit smoking is substantially heritable, with genetics that overlap modestly with the genetics of vulnerability to dependence on addictive substances. Objectives: To identify replicated genes that facilitate smokers' abilities to achieve and sustain abstinence from smoking (hereinafter referred to as quit-success genes) found in more than 2 genome-wide association (GWA) studies of successful vs unsuccessful abstainers, and, secondarily, to nominate genes for selective involvement in smoking cessation success with bupropion hydrochloride vs nicotine replacement therapy (NRT). Design: The GWA results in subjects from 3 centers, with secondary analyses of NRT vs bupropion responders. Setting: Outpatient smoking cessation trial participants from 3 centers. Participants: European American smokers who successfully vs unsuccessfully abstain from smoking with biochemical confirmation in a smoking cessation trial using NRT, bupropion, or placebo (N=550). Main Outcome Measures: Quit-success genes, reproducibly identified by clustered nominally positive single-nucleotide polymorphisms (SNPs) in more than 2 independent samples with significant P values based on Monte Carlo simulation trials. The NRT-selective genes were nominated by clustered SNPs that display much larger t values for NRT vs placebo comparisons. The bupropion-selective genes were nominated by bupropion-selective results. Results: Variants in quit-success genes are likely to alter cell adhesion, enzymatic, transcriptional, structural, and DNA, RNA, and/or protein-handling functions. Quit-success genes are identified by clustered nominally positive SNPs from more than 2 samples and are unlikely to represent chance observations (Monte Carlo P<.0003). These genes display modest overlap with genes identified in GWA studies of dependence on addictive substances and memory. Conclusions: These results support polygenic genetics for success in abstaining from smoking, overlap with genetics of substance dependence and memory, and nominate gene variants for selective influences on therapeutic responses to bupropion vs NRT. Molecular genetics should help match the types and/or intensity of anti-smoking treatments with the smokers most likely to benefit from them. ©2008 American Medical Association. All rights reserved.

Authors
Uhl, GR; Liu, Q-R; Drgon, T; Johnson, C; Walther, D; Rose, JE; David, SP; Niaura, R; Lerman, C
MLA Citation
Uhl, GR, Liu, Q-R, Drgon, T, Johnson, C, Walther, D, Rose, JE, David, SP, Niaura, R, and Lerman, C. "Molecular genetics of successful smoking cessation: Convergent genome-wide association study results." Archives of General Psychiatry 65.6 (2008): 683-693.
PMID
18519826
Source
scival
Published In
Archives of General Psychiatry
Volume
65
Issue
6
Publish Date
2008
Start Page
683
End Page
693
DOI
10.1001/archpsyc.65.6.683

Regional brain activity correlates of nicotine dependence.

Fifteen smokers participated in a study investigating brain correlates of nicotine dependence. Dependence was reduced by having subjects switch to denicotinized cigarettes for 2 weeks while wearing nicotine skin patches. Positron emission tomography (PET) scans assessed regional cerebral metabolic rate for glucose (rCMRglc) after overnight nicotine abstinence on three occasions: (1) at baseline; (2) after 2 weeks of exposure to denicotinized cigarettes+nicotine patches; and (3) 2 weeks after returning to smoking the usual brands of cigarettes. Craving for cigarettes and scores on the Fagerström Test of Nicotine Dependence (FTND) questionnaire decreased at the second session relative to the first and last sessions. Regional brain metabolic activity (normalized to whole brain values) at session 2 also showed a significant decrease in the right hemisphere anterior cingulate cortex. Exploratory post hoc analyses showed that the change in craving across sessions was negatively correlated with the change in rCMRglc in several structures within the brain reward system, including the ventral striatum, orbitofrontal cortex and pons. The between-session difference in thalamus activity (right hemisphere) was positively correlated with the difference in FTND scores. Correlational analyses also revealed that reported smoking for calming effects was associated with a decrease (at session 2) in thalamus activity (bilaterally) and with an increase in amygdala activity (left hemisphere). Reported smoking to enhance pleasurable relaxation was associated with an increase in metabolic activity of the dorsal striatum (caudate, putamen) at session 2. These findings suggest that reversible changes in regional brain metabolic activity occur in conjunction with alterations in nicotine dependence. The results also highlight the likely role of thalamic gating processes as well as striatal reward and corticolimbic regulatory pathways in the maintenance of cigarette addiction.

Authors
Rose, JE; Behm, FM; Salley, AN; Bates, JE; Coleman, RE; Hawk, TC; Turkington, TG
MLA Citation
Rose, JE, Behm, FM, Salley, AN, Bates, JE, Coleman, RE, Hawk, TC, and Turkington, TG. "Regional brain activity correlates of nicotine dependence." Neuropsychopharmacology 32.12 (December 2007): 2441-2452.
PMID
17356570
Source
pubmed
Published In
Neuropsychopharmacology (Nature)
Volume
32
Issue
12
Publish Date
2007
Start Page
2441
End Page
2452
DOI
10.1038/sj.npp.1301379

DRD4 VNTR polymorphism is associated with transient fMRI-BOLD responses to smoking cues.

RATIONALE: A dopamine receptor 4 variable number tandem repeat (DRD4 VNTR) polymorphism has been related to reactivity to smoking cues among smokers, but the effect of this genetic variation on brain responses to smoking cues has not been evaluated. OBJECTIVES: The present study evaluated the relationship between carrying the DRD4 VNTR 7-repeat allele and transient functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent responses to smoking cues among adult dependent cigarette smokers. MATERIALS AND METHODS: Smokers (n = 15) underwent fMRI scanning after 2-h abstinence. During scanning, they viewed visual smoking and control cues. A blood sample was assayed for the DRD4 VNTR polymorphism, and participants were categorized based on whether they carried one or two copies of the 7-repeat allele (DRD4 L, n = 7) or not (DRD4 S, n = 8). RESULTS: Contrasts in brain cue-reactivity (smoking minus control cues) between DRD4 groups were conducted using SPM2. Smoking cues as compared to control cues elicited transient brain responses in right superior frontal gyrus (BA 8/9/10/32), left anterior cingulate gyrus (BA 32), and right cuneus (BA 19). Exposure to smoking cues resulted in greater activation of right superior frontal gyrus (BA 10) and right insula in DRD4 L compared to DRD4 S individuals. By contrast, exposure to smoking cues among DRD4 S individuals resulted in no significant increases in activation compared to DRD4 L individuals. CONCLUSIONS: These brain imaging results suggest that DRD4 VNTR polymorphism is related to transient brain responses to smoking cues in regions subserving executive and somatosensory processes.

Authors
McClernon, FJ; Hutchison, KE; Rose, JE; Kozink, RV
MLA Citation
McClernon, FJ, Hutchison, KE, Rose, JE, and Kozink, RV. "DRD4 VNTR polymorphism is associated with transient fMRI-BOLD responses to smoking cues." Psychopharmacology (Berl) 194.4 (November 2007): 433-441.
PMID
17611740
Source
pubmed
Published In
Psychopharmacology
Volume
194
Issue
4
Publish Date
2007
Start Page
433
End Page
441
DOI
10.1007/s00213-007-0860-6

Multiple brain pathways and receptors underlying tobacco addiction.

Over the last 20 years much progress has been made in understanding the pharmacologic basis of tobacco addiction. In particular, the role of nicotine in reinforcing smoking behavior has been studied from a variety of perspectives. This article discusses two important aspects of this topic: (1) brain pathways underlying tobacco addiction; and (2) the actions of nicotine at nicotinic cholinergic receptors. Recent evidence will be reviewed indicating that nicotine reinforces smoking behavior by acting on more than one subtype of nicotinic receptor. Similarly, the role of several brain pathways in tobacco addiction will be considered. Tobacco addiction may thus be seen as a complex neuropsychopharmacological disorder; further progress in smoking cessation treatment may require that we address the multiple molecular and brain components of this addiction.

Authors
Rose, JE
MLA Citation
Rose, JE. "Multiple brain pathways and receptors underlying tobacco addiction." Biochem Pharmacol 74.8 (October 15, 2007): 1263-1270. (Review)
PMID
17826746
Source
pubmed
Published In
Biochemical Pharmacology
Volume
74
Issue
8
Publish Date
2007
Start Page
1263
End Page
1270
DOI
10.1016/j.bcp.2007.07.039

Increases in impulsivity following smoking abstinence are related to baseline nicotine intake and boredom susceptibility.

Trait impulsivity and response inhibition have been shown to be related to smoking behavior. One measure of response inhibition - antisaccade performance, or the ability to inhibit looking at a novel stimulus - has been shown to be worsened by smoking abstinence, improved by nicotine administration and predictive of smoking cessation outcomes. However, relations between antisaccade performance and measures of trait impulsivity have not been extensively evaluated in smokers. In the present study, twelve dependent smokers (n=12) completed an eye tracking task following smoking as usual and overnight abstinence; and they completed baseline measures of trait impulsivity, smoking history and provided biological samples. As expected, overnight abstinence significantly increased antisaccade errors (p<0.002) while having no effect on prosaccade performance. Abstinence-induced increases in antisaccade errors were positively correlated with baseline plasma cotinine and Sensation Seeking Scale Boredom Susceptibility, and negatively correlated with IQ. These results suggest that smoking abstinence significantly increases errors of response inhibition and that the magnitude of this increase is related to trait impulsivity and nicotine intake variables.

Authors
Pettiford, J; Kozink, RV; Lutz, AM; Kollins, SH; Rose, JE; McClernon, FJ
MLA Citation
Pettiford, J, Kozink, RV, Lutz, AM, Kollins, SH, Rose, JE, and McClernon, FJ. "Increases in impulsivity following smoking abstinence are related to baseline nicotine intake and boredom susceptibility." Addict Behav 32.10 (October 2007): 2351-2357.
PMID
17399907
Source
pubmed
Published In
Addictive Behaviors
Volume
32
Issue
10
Publish Date
2007
Start Page
2351
End Page
2357
DOI
10.1016/j.addbeh.2007.02.004

Selectively reduced responses to smoking cues in amygdala following extinction-based smoking cessation: results of a preliminary functional magnetic resonance imaging study.

Preliminary studies suggest an extinction-based smoking cessation treatment using reduced nicotine content (RNC) cigarettes decreases self-report craving for cigarettes prior to quitting and may be an effective smoking cessation treatment. The aims of this study was to evaluate the effect of an extinction-based smoking cessation treatment on brain responses to smoking cues using blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Sixteen (n = 16) dependent smokers were scanned using BOLD fMRI at baseline, following 2-4 weeks of smoking RNC cigarettes while wearing a 21-mg nicotine patch, and 2-4 weeks following quitting smoking. During scanning, participants viewed smoking-related pictures (e.g. lit cigarette) and pictures of people engaged in everyday activities (e.g. using a stapler). Event-related BOLD responses to smoking and control cues were analyzed in regions of interest (ROIs) known to subserve reward, attention, motivation and emotion. The extinction-based treatment simultaneously attenuated responses to smoking cues in amygdala while potentiating responses to control cues. Exploratory analysis indicated that this pattern was also observed in the thalamus of future abstinent but not relapsing smokers. The results of this preliminary study suggest that an extinction-based treatment for smoking cessation alters brain responses to smoking and control cues in amygdala--a region previously associated with drug cue reactivity and extinction.

Authors
McClernon, FJ; Hiott, FB; Liu, J; Salley, AN; Behm, FM; Rose, JE
MLA Citation
McClernon, FJ, Hiott, FB, Liu, J, Salley, AN, Behm, FM, and Rose, JE. "Selectively reduced responses to smoking cues in amygdala following extinction-based smoking cessation: results of a preliminary functional magnetic resonance imaging study." Addict Biol 12.3-4 (September 2007): 503-512.
PMID
17573781
Source
pubmed
Published In
Addiction Biology
Volume
12
Issue
3-4
Publish Date
2007
Start Page
503
End Page
512
DOI
10.1111/j.1369-1600.2007.00075.x

The effects of foods, beverages, and other factors on cigarette palatability.

While smokers commonly report that various foods and beverages worsen or enhance the taste of cigarettes, the prevalence and diversity of these phenomena have not been studied. We administered an open-ended questionnaire to 209 smokers asking for reports of foods or beverages that worsen or enhance the taste of cigarettes. Commonly reported categories that worsen the taste of cigarettes were fruits/vegetables, noncaffeinated beverages, and dairy products. Commonly reported categories that enhance the taste of cigarettes were caffeinated and alcoholic beverages, and meat products. Regression analyses indicated that increased sensitivity to both taste worsening and enhancing were associated with smoking nonmenthol cigarettes. These findings suggest smoking menthol cigarettes reduces both negative and positive effects of food and beverage consumption on smoking satisfaction - thus "evening out" the smoking experience. Clinical implications and directions for future research are discussed.

Authors
McClernon, FJ; Westman, EC; Rose, JE; Lutz, AM
MLA Citation
McClernon, FJ, Westman, EC, Rose, JE, and Lutz, AM. "The effects of foods, beverages, and other factors on cigarette palatability." Nicotine Tob Res 9.4 (April 2007): 505-510.
PMID
17454706
Source
pubmed
Published In
Nicotine and Tobacco Research (OUP)
Volume
9
Issue
4
Publish Date
2007
Start Page
505
End Page
510
DOI
10.1080/14622200701243177

Guidelines on nicotine dose selection for in vivo research

Rationale: This review provides insight for the judicious selection of nicotine dose ranges and routes of administration for in vivo studies. The literature is replete with reports in which a dosaging regimen chosen for a specific nicotine-mediated response was suboptimal for the species used. In many cases, such discrepancies could be attributed to the complex variables comprising species-specific in vivo responses to acute or chronic nicotine exposure. Objectives: This review capitalizes on the authors' collective decades of in vivo nicotine experimentation to clarify the issues and to identify the variables to be considered in choosing a dosaging regimen. Nicotine dose ranges tolerated by humans and their animal models provide guidelines for experiments intended to extrapolate to human tobacco exposure through cigarette smoking or nicotine replacement therapies. Just as important are the nicotine dosaging regimens used to provide a mechanistic framework for acquisition of drug-taking behavior, dependence, tolerance, or withdrawal in animal models. Results: Seven species are addressed: humans, nonhuman primates, rats, mice, Drosophila, Caenorhabditis elegans, and zebrafish. After an overview on nicotine metabolism, each section focuses on an individual species, addressing issues related to genetic background, age, acute vs chronic exposure, route of administration, and behavioral responses. Conclusions: The selected examples of successful dosaging ranges are provided, while emphasizing the necessity of empirically determined dose-response relationships based on the precise parameters and conditions inherent to a specific hypothesis. This review provides a new, experimentally based compilation of species-specific dose selection for studies on the in vivo effects of nicotine. © 2006 Springer-Verlag.

Authors
Matta, SG; Balfour, DJ; Benowitz, NL; Boyd, RT; Buccafusco, JJ; Caggiula, AR; Craig, CR; Collins, AC; Damaj, MI; Donny, EC; Gardiner, PS; Grady, SR; Heberlein, U; Leonard, SS; Levin, ED; Lukas, RJ; Markou, A; Marks, MJ; McCallum, SE; Parameswaran, N; Perkins, KA; Picciotto, MR; Quik, M; Rose, JE; Rothenfluh, A; Schafer, WR; Stolerman, IP; Tyndale, RF; Wehner, JM; Zirger, JM
MLA Citation
Matta, SG, Balfour, DJ, Benowitz, NL, Boyd, RT, Buccafusco, JJ, Caggiula, AR, Craig, CR, Collins, AC, Damaj, MI, Donny, EC, Gardiner, PS, Grady, SR, Heberlein, U, Leonard, SS, Levin, ED, Lukas, RJ, Markou, A, Marks, MJ, McCallum, SE, Parameswaran, N, Perkins, KA, Picciotto, MR, Quik, M, Rose, JE, Rothenfluh, A, Schafer, WR, Stolerman, IP, Tyndale, RF, Wehner, JM, and Zirger, JM. "Guidelines on nicotine dose selection for in vivo research." Psychopharmacology 190.3 (2007): 269-319.
PMID
16896961
Source
scival
Published In
Psychopharmacology
Volume
190
Issue
3
Publish Date
2007
Start Page
269
End Page
319
DOI
10.1007/s00213-006-0441-0

Molecular genetics of nicotine dependence and abstinence: Whole genome association using 520,000 SNPs

Background: Classical genetic studies indicate that nicotine dependence is a substantially heritable complex disorder. Genetic vulnerabilities to nicotine dependence largely overlap with genetic vulnerabilities to dependence on other addictive substances. Successful abstinence from nicotine displays substantial heritable components as well. Some of the heritability for the ability to quit smoking appears to overlap with the genetics of nicotine dependence and some does not. We now report genome wide association studies of nicotine dependent individuals who were successful in abstaining from cigarette smoking, nicotine dependent individuals who were not successful in abstaining and ethnically-matched control subjects free from substantial lifetime use of any addictive substance. Results: These data, and their comparison with data that we have previously obtained from comparisons of four other substance dependent vs control samples support two main ideas: 1) Single nucleotide polymorphisms (SNPs) whose allele frequencies distinguish nicotine-dependent from control individuals identify a set of genes that overlaps significantly with the set of genes that contain markers whose allelic frequencies distinguish the four other substance dependent vs control groups (p < 0.018). 2) SNPs whose allelic frequencies distinguish successful vs unsuccessful abstainers cluster in small genomic regions in ways that are highly unlikely to be due to chance (Monte Carlo p < 0.00001). Conclusion: These clustered SNPs nominate candidate genes for successful abstinence from smoking that are implicated in interesting functions: cell adhesion, enzymes, transcriptional regulators, neurotransmitters and receptors and regulation of DNA, RNA and proteins. As these observations are replicated, they will provide an increasingly-strong basis for understanding mechanisms of successful abstinence, for identifying individuals more or less likely to succeed in smoking cessation efforts and for tailoring therapies so that genotypes can help match smokers with the treatments that are most likely to benefit them. © 2007 Uhl et al; licensee BioMed Central Ltd.

Authors
Uhl, GR; Liu, Q-R; Drgon, T; Johnson, C; Walther, D; Rose, JE
MLA Citation
Uhl, GR, Liu, Q-R, Drgon, T, Johnson, C, Walther, D, and Rose, JE. "Molecular genetics of nicotine dependence and abstinence: Whole genome association using 520,000 SNPs." BMC Genetics 8 (2007).
PMID
17407593
Source
scival
Published In
BMC Genetics
Volume
8
Publish Date
2007
DOI
10.1186/1471-2156-8-10

Denicotinized cigarettes: A new tool to combat cigarette addiction?

Authors
Rose, JE
MLA Citation
Rose, JE. "Denicotinized cigarettes: A new tool to combat cigarette addiction?." Addiction 102.2 (2007): 181-182.
PMID
17222266
Source
scival
Published In
Addiction
Volume
102
Issue
2
Publish Date
2007
Start Page
181
End Page
182
DOI
10.1111/j.1360-0443.2006.01727.x

Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial.

RATIONALE: Despite established links between nicotine dependence and depression, little research has examined the effects of nicotine on depression symptoms. OBJECTIVE: This study evaluated the acute and chronic effects of transdermal nicotine in nonsmokers with baseline depression symptoms during a 4-week, double-blind, placebo-controlled trial. METHODS: Nonsmokers with scores >or=10 on the Center for Epidemiological Studies Depression scale (CES-D) were recruited from the community. Mood and cognitive performance were measured at baseline (day 0) and at 1, 8, 21, and 28 days. Participants were randomly assigned to wear a placebo or nicotine patch for 4 weeks (3.5 mg/day during weeks 1 and 4; 7 mg/day during weeks 2 and 3). The final sample consisted of 11 nonsmokers with a mean baseline CES-D score of 27.36 (SD=10.53). RESULTS: Salivary nicotine levels indicated the majority of participants were compliant with treatment. Acute nicotine did not alter mood. After adjusting for baseline values, chronic nicotine resulted in a significant decline in CES-D scores at day 8 (3.5 mg/day), but returned to placebo levels by the last visit. This return to baseline levels was coincident with a decrease in nicotine administration from 7 to 3.5 mg/day. A similar trend for improved response inhibition as measured by the Conners Continuous Performance Task was also observed. Reported side effects were infrequent and minimal. CONCLUSION: These findings suggest a role for nicotinic receptor systems in the pathophysiology of depression and that nicotinic compounds should be evaluated for treating depression symptoms.

Authors
McClernon, FJ; Hiott, FB; Westman, EC; Rose, JE; Levin, ED
MLA Citation
McClernon, FJ, Hiott, FB, Westman, EC, Rose, JE, and Levin, ED. "Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial." Psychopharmacology (Berl) 189.1 (November 2006): 125-133.
PMID
16977477
Source
pubmed
Published In
Psychopharmacology
Volume
189
Issue
1
Publish Date
2006
Start Page
125
End Page
133
DOI
10.1007/s00213-006-0516-y

Neuroactive steroids, negative affect, and nicotine dependence severity in male smokers.

RATIONALE: Nicotine administration alters neuroactive steroids in rodent models, and serum levels of the neuroactive steroid DHEAS (dehydroepiandrosterone sulfate) appear to be higher in smokers. These molecules may be relevant to tobacco addiction and affective symptoms. OBJECTIVES: This study aims to investigate DHEAS, allopregnanolone, pregnenolone, and other steroids in male smokers to determine potential associations with nicotine dependence severity and negative affect. MATERIALS AND METHODS: Allopregnanolone and pregnenolone serum levels were determined by gas chromatography/mass spectrometry, while DHEAS and other steroid levels were determined by radioimmunoassay in 28 male smokers. Correlational analyses were performed to determine potential associations with rating measures, including the Fagerstrom Test for Nicotine Dependence (FTND), the addiction subscale of the Ikard Smoking Motivation Questionnaire (ISMQ), the craving item on the Reasons to Smoke (RTS) Questionnaire, and the negative affect and craving subscales of the Shiffman-Jarvik Withdrawal Questionnaire. RESULTS: DHEAS levels were inversely correlated with the negative affect subscale of the Shiffman-Jarvik Withdrawal Questionnaire (r=-0.60, p=0.002) and the RTS craving item (r=-0.43, p=0.03), and tended to be inversely correlated with the FTND scores (r=-0.38, p=0.067) and the ISMQ addiction subscale (r=-0.38, p=0.059), adjusting for age. Allopregnanolone levels were positively correlated with cotinine levels (r=0.57, p=0.006); pregnenolone levels tended to be positively correlated with cotinine levels (r=0.40, p=0.066). CONCLUSIONS: DHEAS levels were inversely correlated with negative affect and craving measures, and may predict nicotine dependence severity. Allopregnanolone levels were positively correlated with cotinine levels, suggesting that this neuroactive steroid may be upregulated in smokers. Neuroactive steroids may represent novel smoking cessation agents.

Authors
Marx, CE; Trost, WT; Shampine, L; Behm, FM; Giordano, LA; Massing, MW; Rose, JE
MLA Citation
Marx, CE, Trost, WT, Shampine, L, Behm, FM, Giordano, LA, Massing, MW, and Rose, JE. "Neuroactive steroids, negative affect, and nicotine dependence severity in male smokers." Psychopharmacology (Berl) 186.3 (June 2006): 462-472.
PMID
16402195
Source
pubmed
Published In
Psychopharmacology
Volume
186
Issue
3
Publish Date
2006
Start Page
462
End Page
472
DOI
10.1007/s00213-005-0226-x

Nicotine and nonnicotine factors in cigarette addiction.

RATIONALE: A great deal of research supports the role of nicotine in cigarette addiction. However, the effectiveness of nicotine replacement therapy (NRT) as a smoking cessation treatment has fallen short of initial hopes. A key reason may be that NRT does not address nonnicotine components of smoking reinforcement. These include constituents that provide reinforcing sensory stimulation, components that minimize excessive irritation from inhaled nicotine and other pharmacologically active compounds in cigarette smoke. OBJECTIVE: Studies using various paradigms to dissociate nicotine from other components of smoking are summarized. RESULTS: Nonnicotine components provide many rewarding effects, often surpassing the direct effects of nicotine. Substitutes for the sensory effects of smoking may be effective in relieving craving for cigarettes and in facilitating smoking cessation. Moreover, techniques for devaluing smoking-related cues may decrease craving and enhance subsequent abstinence. Promising approaches for devaluing smoke cues include extinction-based treatments employing denicotinized cigarettes and the use of nicotinic agonist and/or antagonist treatment during the weeks leading up to a quit attempt. Recent studies suggest that incorporating these approaches into a treatment program may significantly increase smoking abstinence rates. Preliminary findings also suggest that replacement of the effects of monoamine oxidase inhibitors contained in cigarette smoke may enhance quit rates. CONCLUSIONS: While current NRT methods have been the mainstay of smoking cessation treatment and will likely continue to serve a useful role, the next stage of progress will likely entail the development of tools designed with recognition of the importance of nonnicotine components of cigarette smoking.

Authors
Rose, JE
MLA Citation
Rose, JE. "Nicotine and nonnicotine factors in cigarette addiction." Psychopharmacology (Berl) 184.3-4 (March 2006): 274-285. (Review)
PMID
16362402
Source
pubmed
Published In
Psychopharmacology
Volume
184
Issue
3-4
Publish Date
2006
Start Page
274
End Page
285
DOI
10.1007/s00213-005-0250-x

Precessation treatment with nicotine skin patch facilitates smoking cessation.

Nicotine replacement therapy (NRT) is a well-established treatment to aid smoking cessation, and current products recommend using NRT only after quitting smoking. However, theoretical arguments and previous data support the hypothesis that precessation use of NRT might be useful in reducing dependence on inhaled nicotine and serve as a helpful prelude to smoking cessation. The present study explored the use of NRT for 2 weeks before a target quit-smoking date, during which subjects continued to smoke ad libitum. Three experimental conditions varied the nicotine delivery of the cigarettes smoked during these 2 weeks so that we could examine the effects of concurrent nicotine administration on compensatory smoking of low tar and nicotine cigarettes. Subjects smoked (a) their usual brands of cigarettes, (b) conventional low tar and nicotine cigarettes, or (c) denicotinized cigarettes. After the quit date, subjects received pharmacotherapy consisting of various doses of NRT (0, 21, or 42 mg/24-hr) in combination with the nicotinic antagonist mecamylamine (10 mg/day). Results showed that precessation nicotine patch treatment was associated with a significantly higher rate of continuous smoking abstinence at 4 weeks, regardless of cigarette condition. Ad libitum smoking before the target quit date was modulated by nicotine patch treatment, and compensatory increases in smoking low tar and nicotine cigarettes were prevented by concurrent use of nicotine patches. These results suggest that use of NRT before a target quit-smoking date deserves further evaluation as a possible smoking cessation treatment. Moreover, while nicotine patches were well tolerated when subjects smoked nicotine-containing cigarettes, the use of nicotine skin patches with reduced-nicotine cigarettes potentially offers the advantage of increased efficacy without introducing concern about toxic effects of excessive nicotine intake.

Authors
Rose, JE; Behm, FM; Westman, EC; Kukovich, P
MLA Citation
Rose, JE, Behm, FM, Westman, EC, and Kukovich, P. "Precessation treatment with nicotine skin patch facilitates smoking cessation." Nicotine Tob Res 8.1 (February 2006): 89-101.
PMID
16497603
Source
pubmed
Published In
Nicotine and Tobacco Research (OUP)
Volume
8
Issue
1
Publish Date
2006
Start Page
89
End Page
101
DOI
10.1080/14622200500431866

Abstinence-induced changes in self-report craving correlate with event-related FMRI responses to smoking cues.

Drug cues have been shown to activate brain regions involved in attention, motivation, and reward in addicted users. However, as studies have typically measured responses in only one state (ie drug abstinence), it is unclear whether observed activations represent amplification by abstinence or stable responses. Thus, the present study was designed to evaluate the stability of event-related responses to visual drug cues in dependent smokers (n=13) using event-related functional magnetic resonance imaging measures. Imaging was conducted following smoking as usual and following overnight abstinence, and self-reported craving measures were obtained before, during, and after scanning. Analysis of hemodynamic response (HDR) amplitudes in each of 13 regions of interest revealed larger responses to smoking compared to control cues in ventral anterior cingulate gyrus (vACG) and superior frontal gyrus. Responses to smoking cues in these and all other regions revealed no effects of abstinence/satiety, thus supporting the notion that cue-elicited brain responses are relatively stable. However, while the abstinence manipulation did not alter group-level responses to smoking cues, at the individual level, abstinence-induced changes in craving (abstinence minus satiety) were positively correlated with changes in HDR amplitude to smoking cues in frontal regions including left inferior frontal gyrus, left vACG, and bilateral middle frontal gyrus. These results suggest that brain responses to smoking cues, while relatively stable at the group level following short-term abstinence, may be modulated by individual differences in craving in response to abstinence-particularly in regions subserving attention and motivation.

Authors
McClernon, FJ; Hiott, FB; Huettel, SA; Rose, JE
MLA Citation
McClernon, FJ, Hiott, FB, Huettel, SA, and Rose, JE. "Abstinence-induced changes in self-report craving correlate with event-related FMRI responses to smoking cues." Neuropsychopharmacology 30.10 (October 2005): 1940-1947.
PMID
15920499
Source
pubmed
Published In
Neuropsychopharmacology (Nature)
Volume
30
Issue
10
Publish Date
2005
Start Page
1940
End Page
1947
DOI
10.1038/sj.npp.1300780

Immediate antecedents of cigarette smoking in smokers with and without posttraumatic stress disorder: a preliminary study.

Using ambulatory methods for 1 day of monitoring, the authors of this study investigated the association between smoking and situational cues in 63 smokers with posttraumatic stress disorder (PTSD) and 32 smokers without PTSD. Generalized estimating equations contrasted 682 smoking and 444 nonsmoking situations by group status. Smoking was strongly related to craving, positive and negative affect, PTSD symptoms, restlessness, and several situational variables among PTSD smokers. For non-PTSD smokers, the only significant antecedent variables for smoking were craving, drinking coffee, being alone, not being with family, not working, and being around others who were smoking. These results are consistent with previous ambulatory findings regarding mood in smokers but also underscore that, in certain populations, mood and symptom variables may be significantly associated with ad lib smoking.

Authors
Beckham, JC; Feldman, ME; Vrana, SR; Mozley, SL; Erkanli, A; Clancy, CP; Rose, JE
MLA Citation
Beckham, JC, Feldman, ME, Vrana, SR, Mozley, SL, Erkanli, A, Clancy, CP, and Rose, JE. "Immediate antecedents of cigarette smoking in smokers with and without posttraumatic stress disorder: a preliminary study." Exp Clin Psychopharmacol 13.3 (August 2005): 219-228.
PMID
16173885
Source
pubmed
Published In
Experimental and Clinical Psychopharmacology
Volume
13
Issue
3
Publish Date
2005
Start Page
219
End Page
228
DOI
10.1037/1064-1297.13.3.219

Mecamylamine moderates cue-induced emotional responses in smokers.

The nicotinic antagonist, mecamylamine, has been shown to reduce cue-elicited cocaine craving and to aid in smoking cessation. In a within-subjects design, 16 dependent smokers received mecamylamine (10 mg) or placebo capsules on two different days. Subjects imagined smoking urge and non-urge scenarios after smoking their usual brand vs. denicotinized cigarettes. Smoking usual-brand cigarettes produced greater positive effects and mecamylamine blocked heart rate (HR) boost and cigarette sensory impact. Mecamylamine also resulted in greater craving and less calmness, regardless of cigarette smoked. Urge script imagination in the mecamylamine+denicotinized condition resulted in calmness similar to usual-brand conditions and higher than the placebo+denicotinized condition. A similar trend was observed for negative affect. These results suggest that mecamylamine can moderate smoking cue-induced emotional responses in smokers.

Authors
McClernon, FJ; Rose, JE
MLA Citation
McClernon, FJ, and Rose, JE. "Mecamylamine moderates cue-induced emotional responses in smokers." Addict Behav 30.4 (May 2005): 741-753.
PMID
15833578
Source
pubmed
Published In
Addictive Behaviors
Volume
30
Issue
4
Publish Date
2005
Start Page
741
End Page
753
DOI
10.1016/j.addbeh.2004.08.020

The effects of trauma recall on smoking topography in posttraumatic stress disorder and non-posttraumatic stress disorder trauma survivors.

Smoking topography was measured in trauma survivors with and without posttraumatic stress disorder (PTSD) after recalling trauma-related and neutral experiences. Analysis of covariance was performed on puff topography and mood measures using nicotine dependence scores and current major depressive disorder as covariates. Puff volumes were higher in the PTSD group than in the non-PTSD group. The PTSD group exhibited stable puff onset intervals while the non-PTSD group exhibited significantly shorter intervals following trauma recall. These findings support a "ceiling effect" hypothesis in which individuals with PTSD perpetually smoke in such a way as to maximize nicotine delivery, possibly reducing the potentially reinforcing effects of increased smoke delivery in negative affect-inducing situations.

Authors
McClernon, FJ; Beckham, JC; Mozley, SL; Feldman, ME; Vrana, SR; Rose, JE
MLA Citation
McClernon, FJ, Beckham, JC, Mozley, SL, Feldman, ME, Vrana, SR, and Rose, JE. "The effects of trauma recall on smoking topography in posttraumatic stress disorder and non-posttraumatic stress disorder trauma survivors." Addict Behav 30.2 (February 2005): 247-257.
PMID
15621396
Source
pubmed
Published In
Addictive Behaviors
Volume
30
Issue
2
Publish Date
2005
Start Page
247
End Page
257
DOI
10.1016/j.addbeh.2004.05.013

Ethics of tobacco company funding [3]

Authors
Rose, JE
MLA Citation
Rose, JE. "Ethics of tobacco company funding [3]." Science 308.5722 (2005): 632--.
PMID
15860608
Source
scival
Published In
Science
Volume
308
Issue
5722
Publish Date
2005
Start Page
632-

Development of a system for the non-invasive measurement of the time course of [C-11] nicotine

It is widely believed that the addictive effects of cigarette smoking derive largely from the rapid absorption of nicotine from the pulmonary system. The immediate effects of an inhaled bolus of nicotine on brain function are thought to provide potent reinforcement for smoking behavior and maintain dependence on tobacco. A greater understanding of the initial time course of nicotine in arterial blood may be useful in achieving a greater understanding of smoking behavior. An experimental system that non-invasively measures the initial time course of [C-11] nicotine in the body has been developed. This apparatus observes the inhalation of [C-11] nicotine injected into a cigarette and the arrival of [C-11] nicotine at four locations in the body: the throat, lungs, brain, and wrist. NaI(Tl) scintillation crystals (3" × 3") are used as coincident radiation detectors. Event pulses are processed to provide energy discrimination and processed with coincidence logic. Conservative calculations predict that 1 mCi of [C-11] nicotine will produce between 200 and 1500 coincidences per second in the four regions which allows the measurement of the arrival times with 0.5s precision. The inhalation of the [C-11] nicotine is measured by a plastic scintillator detector placed around the cigarette. The observation of the decrease in activity in the cigarette provides an accurate identification of inhalation time. © 2005 IEEE.

Authors
Lokitz, SJ; Rose, JE; Turkington, TG
MLA Citation
Lokitz, SJ, Rose, JE, and Turkington, TG. "Development of a system for the non-invasive measurement of the time course of [C-11] nicotine." IEEE Nuclear Science Symposium Conference Record 3 (2005): 1795-1799.
Source
scival
Published In
IEEE Nuclear Science Symposium Conference Record
Volume
3
Publish Date
2005
Start Page
1795
End Page
1799
DOI
10.1109/NSSMIC.2005.1596669

The effects of controlled deep breathing on smoking withdrawal symptoms in dependent smokers.

This study was designed to assess the effect of controlled deep breathing on smoking withdrawal symptoms. In two laboratory sessions, dependent smokers refrained from smoking for 4 h. During a deep breathing session, participants were instructed to take a series of deep breaths every 30 min. During a control session, participants sat quietly. Controlled deep breathing significantly reduced smoking withdrawal symptoms, including craving for cigarettes and negative affect (tense, irritable), while resulting in the maintenance of baseline arousal (wide awake, able to concentrate) levels. Furthermore, a history of heavy smoking was associated with greater increases in arousal during the deep breathing session. The results of this preliminary study suggest that controlled deep breathing may be useful for relieving symptoms of smoking withdrawal.

Authors
McClernon, FJ; Westman, EC; Rose, JE
MLA Citation
McClernon, FJ, Westman, EC, and Rose, JE. "The effects of controlled deep breathing on smoking withdrawal symptoms in dependent smokers." Addict Behav 29.4 (June 2004): 765-772.
PMID
15135559
Source
pubmed
Published In
Addictive Behaviors
Volume
29
Issue
4
Publish Date
2004
Start Page
765
End Page
772
DOI
10.1016/j.addbeh.2004.02.005

Extinguishing the rewarding value of smoke cues: pharmacological and behavioral treatments.

The present study examined several pharmacological and behavioral treatments designed to promote extinction of the responses to rewarding cigarette smoke cues. Pharmacological treatments comprised nicotine skin patches (21 mg/24 hr) and the nicotinic acetylcholine receptor antagonist mecamylamine (10 mg/day), administered separately or in combination. Behavioral manipulations included switching to denicotinized cigarettes, to cigarettes having different menthol flavor, or to ventilated-filter (low tar and nicotine) cigarettes. Smokers were assigned to the various treatments for 2 weeks before they quit smoking. During weekly test sessions, subjects rated the rewarding effects of their usual brands of cigarettes or cigarettes with different menthol content (mentholated vs. nonmentholated). Over the 2-week treatment period, all pharmacological treatments reduced ratings of reward for the usual-brand test cigarettes. Switching to smoking denicotinized cigarettes for 2 weeks similarly decreased rewarding effects of the usual-brand test cigarettes. Subjects also strongly preferred cigarettes with the same menthol content to which they were accustomed. However, manipulating the menthol content of the cigarettes smoked during the 2 weeks of treatment had different effects, depending on whether smokers habitually smoked mentholated or nonmentholated cigarettes. For menthol smokers, removal of the menthol cue hampered extinction of reward ratings for the usual-brand (mentholated) test cigarette. For nonmenthol smokers, addition of the menthol cue did not affect the progress of extinction of nonmenthol smoke cues. These findings demonstrate the importance of sensory cues in determining subjective reward and show that the reward value of these cues can be altered by removal of nicotine from tobacco or by pharmacological manipulations that interfere with the reinforcing effects of nicotine.

Authors
Rose, JE; Behm, FM
MLA Citation
Rose, JE, and Behm, FM. "Extinguishing the rewarding value of smoke cues: pharmacological and behavioral treatments." Nicotine Tob Res 6.3 (June 2004): 523-532.
PMID
15203786
Source
pubmed
Published In
Nicotine and Tobacco Research (OUP)
Volume
6
Issue
3
Publish Date
2004
Start Page
523
End Page
532
DOI
10.1080/14622200410001696501

Psychopharmacological interactions between nicotine and ethanol.

Epidemiological, clinical, and laboratory evidence has shown a positive correlation between cigarette smoking and ethanol use, and previous studies suggest some commonality in the neural pathways mediating effects of nicotine and ethanol. In this study, the subjective and behavioral interactions among nicotine, ethanol, and the nicotinic antagonist mecamylamine were investigated. The main objectives were to determine how the rewarding effects of nicotine might be modified by ethanol, and to compare the effects of ethanol with those of a nicotinic antagonist (mecamylamine). A total of 48 smokers who regularly consumed alcoholic beverages participated in four laboratory sessions presenting a 2 (nicotine vs. denicotinized cigarette smoke)x2 (10 mg oral mecamylamine hydrochloride vs. placebo)x2 (ethanol.5 g/kg vs. placebo) design, with ethanol as a between-subjects factor. Dependent measures included blood alcohol concentration (BAC), as assessed by breath alcohol detector; subjective drug effects; and rate of ad lib smoking during a 2-hr period. Results showed that peak BAC averaged.03 g/dl in the ethanol condition. Ethanol potentiated some of the subjective rewarding effects of nicotine, including smoking satisfaction, stimulant as well as calming effects, and relief of craving for cigarettes. During the ad lib smoking period, mecamylamine decreased satisfaction associated with the nicotine-containing cigarettes; mecamylamine also induced smoking but only in the placebo ethanol condition. These results highlight the potent interaction between ethanol and nicotinic systems, and suggest that ethanol can potentiate the rewarding effects of nicotine as well as offset some of the effects of a nicotinic antagonist.

Authors
Rose, JE; Brauer, LH; Behm, FM; Cramblett, M; Calkins, K; Lawhon, D
MLA Citation
Rose, JE, Brauer, LH, Behm, FM, Cramblett, M, Calkins, K, and Lawhon, D. "Psychopharmacological interactions between nicotine and ethanol." Nicotine Tob Res 6.1 (February 2004): 133-144.
PMID
14982697
Source
pubmed
Published In
Nicotine and Tobacco Research (OUP)
Volume
6
Issue
1
Publish Date
2004
Start Page
133
End Page
144
DOI
10.1080/14622200310001656957

Erratum: "Effects of low nicotine content cigarettes on smoke intake" (Nicotine & Tobacco Research (2004) vol. 6 (2) (309-319))

Authors
Rose, JE; Behm, FM
MLA Citation
Rose, JE, and Behm, FM. "Erratum: "Effects of low nicotine content cigarettes on smoke intake" (Nicotine & Tobacco Research (2004) vol. 6 (2) (309-319))." Nicotine and Tobacco Research 6.3 (2004): 575--.
Source
scival
Published In
Nicotine and Tobacco Research
Volume
6
Issue
3
Publish Date
2004
Start Page
575-
DOI
10.1080/14622200410001703160

Effects of low nicotine content cigarettes on smoke intake

Cigarettes with selective reductions in nicotine delivery have been considered as potential tools to prevent or treat nicotine dependence or to reduce harm by virtue of reduced nicotine and nitrosamine delivery. An important question is whether individuals smoke these products more intensively, as has been shown to occur with ventilated-filter cigarettes. To investigate this issue, we compared conventional highly ventilated filter cigarettes, having very low tar and nicotine yields when smoked by Federal Trade Commission method (1 mg tar, 2 mg carbon monoxide [CO], .2 mg nicotine), with low nicotine content cigarettes, manufactured from a genetically modified strain of tobacco, which had higher tar but lower nicotine yield (14mg tar, 13mg CO, .02mg nicotine). A total of 16 cigarette smokers participated in two 8-hr sessions (order counterbalanced) during which they smoked each type of cigarette ad libitum. Expired-air CO, plasma nicotine, and smoking topography measures were collected. Subjects showed significant increases in smoking when using the highly ventilated filter cigarettes, and puff volume was significantly greater than with the low nicotine content cigarettes. Subjects achieved an expired-air CO level 74% as high as with the low nicotine content cigarettes; the latter produced CO levels similar to those measured at baseline when subjects smoked their habitual brands of cigarettes. Plasma nicotine levels obtained when subjects smoked the highly ventilated filter cigarettes also were significantly higher than when they smoked the low nicotine content cigarettes. These results indicate that the delivery of substantial amounts of smoke, with selective reductions in nicotine yield, appears to prevent compensatory smoking behavior. Further studies should determine whether similar results are obtained in naturalistic environments. © 2004 Society for Research on Nicotine and Tobacco.

Authors
Rose, JE; Behm, FM
MLA Citation
Rose, JE, and Behm, FM. "Effects of low nicotine content cigarettes on smoke intake." Nicotine and Tobacco Research 6.2 (2004): 309-319.
PMID
15203805
Source
scival
Published In
Nicotine and Tobacco Research
Volume
6
Issue
2
Publish Date
2004
Start Page
309
End Page
319
DOI
10.1080/14622200410001676378

Adolescent-onset nicotine self-administration modeled in female rats.

RATIONALE: Although the great majority of tobacco addiction begins during adolescence, little is known about differential nicotine effects in adolescents versus adults. OBJECTIVES: A rat model was used to determine the impact of the age of onset on nicotine self-administration. METHODS: In expt 1, nicotine self-administration of female Sprague-Dawley rats over a range of acute doses (0.01-0.08 mg/kg per infusion) was determined in adolescent (beginning at 54-62 days) versus adult (beginning at 84-90 days). In expt 2, chronic nicotine self-administration over 4 weeks from adolescence into adulthood was compared with the chronic self-administration beginning in adulthood. In expt 3, adolescent-adult differences in nicotine effects on body temperature and locomotor responses were determined. RESULTS: Adolescent-onset rats showed a significant main effect of increased nicotine intake compared with adult-onset rats in an eight-fold range of acute unit doses/infusion. Significant age differences were also seen in the chronic level of nicotine self-administration. Over 4 weeks, the adolescent-onset group had nearly double the rate of nicotine self-administration of the benchmark nicotine dose (0.03 mg/kg per infusion) compared to the adult-onset group. This increased nicotine intake persisted into adulthood. Adolescent rats had significantly greater response than adults to the hypothermic effects of nicotine, but had significantly less response than adults to the reduction in locomotor activity seen after nicotine. CONCLUSIONS: Adolescent-onset nicotine self-administration in female rats was associated with significantly higher levels of nicotine self-administration versus rats, which began nicotine self-administration in adulthood. This greater self-administration persists into adulthood and may underlie greater propensity of adolescents to nicotine addiction.

Authors
Levin, ED; Rezvani, AH; Montoya, D; Rose, JE; Swartzwelder, HS
MLA Citation
Levin, ED, Rezvani, AH, Montoya, D, Rose, JE, and Swartzwelder, HS. "Adolescent-onset nicotine self-administration modeled in female rats." Psychopharmacology (Berl) 169.2 (September 2003): 141-149.
PMID
12764575
Source
pubmed
Published In
Psychopharmacology
Volume
169
Issue
2
Publish Date
2003
Start Page
141
End Page
149
DOI
10.1007/s00213-003-1486-y

Pharmacologic and sensorimotor components of satiation in cigarette smoking.

To examine mechanisms underlying satiation in cigarette smoking, 18 smokers received intravenous (i.v.) nicotine, alone or in combination with denicotinized cigarette smoke. Nicotine was administered using programmed presentations of either pulsed injections or continuous infusions, with i.v. saline serving as a control. A high-nicotine cigarette smoke condition (usual brand) was also presented. During each of the six test sessions, subjects were allowed to puff on their usual brands of cigarette ad libitum while the programmed satiation conditions were in force. Administration of i.v. nicotine caused a small suppression of ad libitum smoking behavior; denicotinized smoke produced a significantly larger reduction, showing that short-term satiation is more dependent on the presentation of smoke than delivery of nicotine per se. However, denicotinized smoke alone did not have as much effect as puffs from the usual brands of cigarettes. The combination of i.v. nicotine and denicotinized smoke puffs produced equivalent satiation to that of the usual brand. Cigarette craving and negative affect were partially relieved by iv nicotine presentations as well as by denicotinized smoke, and again the combination of i.v. nicotine and denicotinized smoke approximated the effects of the usual brand. The results of this study underscore the importance of both sensorimotor aspects of smoking and the pharmacologic effects of nicotine in tobacco dependence.

Authors
Rose, JE; Behm, FM; Westman, EC; Bates, JE; Salley, A
MLA Citation
Rose, JE, Behm, FM, Westman, EC, Bates, JE, and Salley, A. "Pharmacologic and sensorimotor components of satiation in cigarette smoking." Pharmacol Biochem Behav 76.2 (September 2003): 243-250.
PMID
14592675
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
76
Issue
2
Publish Date
2003
Start Page
243
End Page
250

Mecamylamine acutely increases human intravenous nicotine self-administration.

Previous studies of human cigarette smoking have shown that administration of the nicotinic acetylcholine receptor antagonist mecamylamine produces acute increases in smoking behavior. In contrast, studies of intravenous nicotine self-administration in animals typically show an immediate decrease in self-administration behavior following mecamylamine administration. To investigate whether this discrepancy might be due in part to the mode of nicotine self-administration (intravenous vs. cigarette smoke), we measured the rate of intravenous nicotine self-administration in tobacco-dependent human smokers. After being trained in a preliminary session to self-administer puff-sized bolus doses of nicotine, 16 subjects were exposed to two sessions (4 h duration) in which they could self-administer intravenous nicotine ad lib. Two hours prior to one session, subjects swallowed a capsule containing 10 mg mecamylamine, and before the other session they took a placebo capsule. Rates of responding for nicotine were assessed, as were subjective reports of withdrawal symptoms and plasma nicotine levels. There was a significantly higher rate of nicotine self-administration in the mecamylamine condition, and mecamylamine attenuated the reduction in craving over the session that occurred during nicotine self-administration. These results indicate that route of administration is not likely the major source of the discrepancy between findings from animal and human studies of nicotine administration. Instead, it is likely that the higher rates of nicotine self-administration induced by mecamylamine were due to an attenuation of the effects of nicotine (e.g., alleviation of withdrawal symptoms) in nicotine-dependent subjects. Thus, animal models of nicotine dependence may need to be employed in conjunction with self-administration procedures in order to duplicate the effects of mecamylamine observed in studies of human smokers.

Authors
Rose, JE; Behm, FM; Westman, EC; Bates, JE
MLA Citation
Rose, JE, Behm, FM, Westman, EC, and Bates, JE. "Mecamylamine acutely increases human intravenous nicotine self-administration." Pharmacol Biochem Behav 76.2 (September 2003): 307-313.
PMID
14592683
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
76
Issue
2
Publish Date
2003
Start Page
307
End Page
313

Reliabilities and intercorrelations of reported and objective measures of smoking in patients with schizophrenia.

We examined the test-retest reliabilities of reported and objective measures of smoking, and the intercorrelations among these measures, in acutely psychotic patients with schizophrenia to determine whether severe psychiatric illness affects the utility of these variables. All measures demonstrated good test-retest reliability. Objective measures of smoking were consistently intercorrelated and should be the preferred outcome measures in studies testing strategies to reduce smoking.

Authors
Yang, YK; McEvoy, JP; Wilson, WH; Levin, ED; Rose, JE
MLA Citation
Yang, YK, McEvoy, JP, Wilson, WH, Levin, ED, and Rose, JE. "Reliabilities and intercorrelations of reported and objective measures of smoking in patients with schizophrenia." Schizophr Res 60.1 (March 1, 2003): 9-12.
PMID
12505133
Source
pubmed
Published In
Schizophrenia Research
Volume
60
Issue
1
Publish Date
2003
Start Page
9
End Page
12

PET studies of the influences of nicotine on neural systems in cigarette smokers.

OBJECTIVE: The effects of acute nicotine administration and smoking on brain function were investigated in two studies, with the primary goal of identifying neural systems that mediate these effects. METHOD: In study 1, 18 healthy volunteer cigarette smokers were exposed to three conditions in a single session: 1) smoking a nicotine-containing cigarette, 2) smoking a denicotinized cigarette, or 3) receiving intravenous nicotine injections in conjunction with smoking a denicotinized cigarette. In study 2, 16 subjects smoked a nicotine-containing and denicotinized cigarette in each of two sessions 2 hours after receiving the nicotinic antagonist mecamylamine (10 mg) or placebo orally. Regional cerebral blood flow (rCBF) was assessed by using the bolus (15)O-labeled water method and positron emission tomography. Subjective measures of smoking withdrawal symptoms were also collected. RESULTS: A principal-components analysis of rCBF data pooled from the two studies identified three factors consisting of frontal, striatal, and reticular systems. The amygdala was considered as a separate region of interest. Nicotine increased normalized rCBF in the left frontal region and decreased rCBF in the left amygdala. The rCBF in the right hemisphere reticular system was related to nicotine dose in an inverted-U-shaped pattern and was strongly related to self-reported craving for cigarettes and to the addiction scale of a smoking motivation questionnaire. The effects of mecamylamine on rCBF were generally opposite to those of nicotine. CONCLUSIONS: The results indicate that nicotine influences brain regions involved in arousal and reward and suggest specific functional systems that may be linked to motivationally significant aspects of tobacco dependence.

Authors
Rose, JE; Behm, FM; Westman, EC; Mathew, RJ; London, ED; Hawk, TC; Turkington, TG; Coleman, RE
MLA Citation
Rose, JE, Behm, FM, Westman, EC, Mathew, RJ, London, ED, Hawk, TC, Turkington, TG, and Coleman, RE. "PET studies of the influences of nicotine on neural systems in cigarette smokers." Am J Psychiatry 160.2 (February 2003): 323-333.
PMID
12562580
Source
pubmed
Published In
American Journal of Psychiatry
Volume
160
Issue
2
Publish Date
2003
Start Page
323
End Page
333
DOI
10.1176/appi.ajp.160.2.323

Potentiation of nicotine reward by alcohol.

Authors
Rose, JE; Brauer, LH; Behm, FM; Cramblett, M; Calkins, K; Lawhon, D
MLA Citation
Rose, JE, Brauer, LH, Behm, FM, Cramblett, M, Calkins, K, and Lawhon, D. "Potentiation of nicotine reward by alcohol." Alcohol Clin Exp Res 26.12 (December 2002): 1930-1931.
PMID
12500124
Source
pubmed
Published In
Alcoholism: Clinical and Experimental Research
Volume
26
Issue
12
Publish Date
2002
Start Page
1930
End Page
1931
DOI
10.1097/01.ALC.0000040982.92057.52

Haloperidol reduces smoking of both nicotine-containing and denicotinized cigarettes

Rationale: Studies with laboratory animals and humans suggest that dopamine may play a role in maintaining cigarette smoking behavior via its interactions with nicotine. Objectives: This study was designed to replicate and extend previous findings showing that the dopamine D2 antagonist, haloperidol, produces blockade of smoking reward and compensatory increases in smoking. Methods: We studied 20 subjects in a 2×3 within-subjects design, with nicotine-containing or denicotinized cigarettes crossed with oral placebo, haloperidol 1 mg, or haloperidol 2 mg. Subjects attended six sessions during which they received one of the cigarette/drug combinations, and smoked under both controlled and ad libitum conditions. Cigarette and mood ratings and smoking behavior were assessed. Results: Haloperidol reduced the number of cigarettes smoked and the carbon monoxide boost associated with both types of cigarettes, at doses that did not appear to produce clinically significant behavioral effects. Conclusions: Dopamine appears to play a role in mediating smoking behavior, but this may occur through a non-nicotine mechanism.

Authors
Brauer, LH; Cramblett, MJ; Paxton, DA; Rose, JE
MLA Citation
Brauer, LH, Cramblett, MJ, Paxton, DA, and Rose, JE. "Haloperidol reduces smoking of both nicotine-containing and denicotinized cigarettes." Psychopharmacology 159.1 (2002): 31-37.
PMID
11797066
Source
scival
Published In
Psychopharmacology
Volume
159
Issue
1
Publish Date
2002
Start Page
31
End Page
37
DOI
10.1007/s002130100894

Mecamylamine modifies the pharmacokinetics and reinforcing effects of alcohol

Background: Central nicotinic cholinergic receptors modify alcohol-induced mesolimbic dopamine activation, which seems to be important in the reinforcing properties of alcohol. Consistent with this model, acute administration to rats of the tertiary nicotinic receptor antagonist mecamylamine blocks both alcohol consumption and alcohol-induced dopamine release in the nucleus accumbens. This study was conducted to test the hypothesis that, during the ascending limb of the blood alcohol concentration curve, mecamylamine would reduce the stimulating and pleasurable effects of an intoxicating dose of alcohol in humans. Methods: Ten female and 10 male volunteers with no history of alcohol or substance use disorders, including nicotine dependence, completed the study. During two laboratory sessions, subjects consumed three aliquots of an alcohol-containing drink, with a total ethanol content of 0.7 g/kg (in women) or 0.8 g/kg (in men), over a 30-min period. Two hours before the first drink, subjects were pretreated with mecamylamine or placebo, with the order of sessions counterbalanced. Primary outcome measures included the Drug Effect Questionnaire, the central stimulation subscale of the Alcohol Sensation Scale, and the stimulant subscale of the Biphasic Alcohol Effects Scale. Breath alcohol level (BAL) was examined to identify the ascending and descending limbs of the blood alcohol curve and to assess pharmacokinetic interactions between alcohol and mecamylamine. Results: Significant effects of time, study drug, and their interaction were observed. Compared with placebo, mecamylamine reduced BAL. After controlling for BAL at each time point, mecamylamine also reduced the Drug Effect Questionnaire and Alcohol Sensation Scale stimulant subscale scores, with a trend for a similar effect on the Biphasic Alcohol Effects Scale score. Conclusions: Mecamylamine seems to modify both the pharmacokinetic profile of alcohol and the rewarding effects of alcohol in healthy volunteers.

Authors
Blomqvist, O; Hernandez-Avila, CA; Kirk, JV; Rose, JE; Kranzler, HR
MLA Citation
Blomqvist, O, Hernandez-Avila, CA, Kirk, JV, Rose, JE, and Kranzler, HR. "Mecamylamine modifies the pharmacokinetics and reinforcing effects of alcohol." Alcoholism: Clinical and Experimental Research 26.3 (2002): 326-331.
PMID
11923584
Source
scival
Published In
Alcoholism: Clinical and Experimental Research
Volume
26
Issue
3
Publish Date
2002
Start Page
326
End Page
331

Oral nicotine solution for smoking cessation: a pilot tolerability study.

This study was conducted to determine the preliminary tolerability of an oral nicotine solution with minimal behavioral intervention for smoking cessation. Twenty-five healthy volunteers who smoked at least 10 cigarettes per day and were motivated to quit smoking were enrolled in an open-labeled trial with a 12-week treatment and a 6-month follow-up period. After reviewing self-help materials and setting a quit-smoking day, subjects were provided nicotine solution to mix with their beverages to control smoking urges, and returned for refills eight times over 12 weeks. Abstinence (point prevalence) was defined as self-report of 0 cigarettes smoked for the previous 7 days verified by exhaled carbon monoxide (CO) <10 ppm. The oral nicotine solution was well tolerated when mixed with an individual's chosen beverage. Subjects controlled the concentration of nicotine consumed, which ranged from 0.25 to 10 mg nicotine base per 170-354 ml of beverage. One week after the quit date the mean venous nicotine level was 13.4 ng/ml and mean serum cotinine level was 418.0 ng/ml in six non-smokers. Abstinence rates at 4 weeks, 3 months, and 6 months were 28.0%, 24.0%, and 20.0%, respectively. It was concluded that an oral nicotine solution was tolerable and provided nicotine replacement at levels that may prove useful for smoking cessation. Further research to clarify appropriate dosages and optimal beverages for mixture, and controlled trials to assess safety and efficacy, appear in order.

Authors
Westman, EC; Tomlin, KF; Perkins, CE; Rose, JE
MLA Citation
Westman, EC, Tomlin, KF, Perkins, CE, and Rose, JE. "Oral nicotine solution for smoking cessation: a pilot tolerability study." Nicotine Tob Res 3.4 (November 2001): 391-396.
PMID
11694207
Source
pubmed
Published In
Nicotine and Tobacco Research (OUP)
Volume
3
Issue
4
Publish Date
2001
Start Page
391
End Page
396
DOI
10.1080/14622200110050400

Platelet monoamine oxidase, smoking cessation, and tobacco withdrawal symptoms.

Previous studies have found that constituents in tobacco inhibit both forms of the enzyme monoamine oxidase (MAO-A and MAO-B). This enzyme is important in the breakdown of the amine neurotransmitters, including dopamine, which is thought to mediate the reinforcing effects of nicotine and contribute to tobacco dependence. To further examine the relationship between cigarette smoking, smoking cessation and MAO, we measured platelet MAO-B activity in 16 smokers before and after being switched to smoking denicotinized cigarettes; in a subset of six subjects who subsequently quit-smoking, MAO-B activity was also measured at 1 and 4 weeks following cessation. Smoking cessation treatment was provided in an open-label format, and included nicotine skin patch treatment in conjunction with oral mecamylamine (a nicotinic antagonist) and neostigmine (a peripherally acting acetylcholinesterase inhibitor, administered to counteract constipation experienced from mecamylamine). Results showed that smoking behavior, indexed by expired air carbon monoxide levels, was negatively correlated with platelet MAO-B activity prior to smoking cessation. Moreover, MAO-B activity significantly increased by approximately 100% at 4 weeks after quitting smoking. However, little or no recovery occurred within the first week of abstinence, suggesting that the constituents in tobacco responsible for MAO inhibition may have half-lives of several days. Thus, if relapse to smoking is due in part to withdrawal from the MAO-inhibiting effects of tobacco, this effect likely occurs more than 1 week after quitting. Additionally, low baseline MAO-B activity significantly predicted the intensity of withdrawal symptoms reported upon switching to the denicotinized cigarettes as well as after smoking cessation. These results support the view that MAO inhibition from non-nicotine constituents in cigarette smoke is relevant to tobacco dependence and that continued investigation of the potential use of MAO inhibitors in smoking cessation treatment is warranted.

Authors
Rose, JE; Behm, FM; Ramsey, C; Ritchie, JC
MLA Citation
Rose, JE, Behm, FM, Ramsey, C, and Ritchie, JC. "Platelet monoamine oxidase, smoking cessation, and tobacco withdrawal symptoms." Nicotine Tob Res 3.4 (November 2001): 383-390.
PMID
11694206
Source
pubmed
Published In
Nicotine and Tobacco Research (OUP)
Volume
3
Issue
4
Publish Date
2001
Start Page
383
End Page
390
DOI
10.1080/14622200110087277

Individual differences in smoking reward from de-nicotinized cigarettes.

Most studies of cigarette smoking and smoking cessation have focused on the psychopharmacological effects of nicotine; relatively few have explored the role of sensory aspects of cigarette smoke. Sensory aspects of cigarette smoke play a role in the maintenance of smoking behavior, and may be particularly important for certain smokers. This paper presents the results of a pooled analysis of nine studies conducted in our laboratory, in order to explore the influence of demographic and smoking-related variables on ratings of de-nicotinized as compared to nicotine-containing cigarettes. A major finding of this analysis is that ratings of smoking derived from de-nicotinized, but not nicotine-containing, cigarettes appear to vary with level of tobacco dependence, suggesting that sensory factors may be more important to highly dependent, as compared to less-dependent, smokers. The implications of these findings for smoking cessation treatment and for future research are discussed.

Authors
Brauer, LH; Behm, FM; Lane, JD; Westman, EC; Perkins, C; Rose, JE
MLA Citation
Brauer, LH, Behm, FM, Lane, JD, Westman, EC, Perkins, C, and Rose, JE. "Individual differences in smoking reward from de-nicotinized cigarettes." Nicotine Tob Res 3.2 (May 2001): 101-109. (Review)
PMID
11403723
Source
pubmed
Published In
Nicotine and Tobacco Research (OUP)
Volume
3
Issue
2
Publish Date
2001
Start Page
101
End Page
109
DOI
10.1080/14622200110042000

Acute effects of nicotine and mecamylamine on tobacco withdrawal symptoms, cigarette reward and ad lib smoking.

Separate and combined effects of nicotine and the nicotinic antagonist mecamylamine were studied in 32 healthy volunteer smokers after overnight abstinence from smoking. Subjects participated in three sessions (3 h each), during which they wore skin patches delivering either 0 mg/24 h, 21 mg/24 h or 42 mg/24 h nicotine. Thirty-two subjects were randomly assigned to two groups receiving oral mecamylamine hydrochloride (10 mg) vs. placebo capsules. Two and one-half hours after drug administration, subjects were allowed to smoke ad lib, rating the cigarettes for rewarding and aversive effects. Transdermal nicotine produced a dose-related reduction in the subjective rewarding qualities of smoking. Nicotine also reduced craving for cigarettes and this effect was attenuated, but not eliminated, by mecamylamine. Mecamylamine blocked the discriminability of high vs. low nicotine puffs of smoke, and increased nicotine intake substantially during the ad lib smoking period. Some of the psychophysiological effects of each drug (elevation in blood pressure from nicotine, sedation and decreased blood pressure from mecamylamine) were offset by the other drug. The results supported the hypothesis that nicotine replacement can alleviate tobacco withdrawal symptoms even in the presence of an antagonist such as mecamylamine. Mecamylamine did not precipitate withdrawal beyond the level associated with overnight cigarette deprivation, suggesting its effects were primarily due to offsetting the action of concurrently administered nicotine as opposed to blocking endogenous cholinergic transmission.

Authors
Rose, JE; Behm, FM; Westman, EC
MLA Citation
Rose, JE, Behm, FM, and Westman, EC. "Acute effects of nicotine and mecamylamine on tobacco withdrawal symptoms, cigarette reward and ad lib smoking." Pharmacol Biochem Behav 68.2 (February 2001): 187-197.
PMID
11267622
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
68
Issue
2
Publish Date
2001
Start Page
187
End Page
197

The effects of trauma recall on smoking topography in posttraumatic stress disorder and non-posttraumatic stress disorder trauma survivors

Smoking topography was measured in trauma survivors with and without posttraumatic stress disorder (PTSD) after recalling trauma-related and neutral experiences. Analysis of covariance was performed on puff topography and mood measures using nicotine dependence scores and current major depressive disorder as covariates. Puff volumes were higher in the PTSD group than in the non-PTSD group. The PTSD group exhibited stable puff onset intervals while the non-PTSD group exhibited significantly shorter intervals following trauma recall. These findings support a "ceiling effect" hypothesis in which individuals with PTSD perpetually smoke in such a way as to maximize nicotine delivery, possibly reducing the potentially reinforcing effects of increased smoke delivery in negative affect-inducing situations. © 2004 Elsevier Ltd. All rights reserved.

Authors
McClernon, FJ; Beckham, JC; Mozley, SL; Feldman, ME; Vrana, SR; Rose, JE
MLA Citation
McClernon, FJ, Beckham, JC, Mozley, SL, Feldman, ME, Vrana, SR, and Rose, JE. "The effects of trauma recall on smoking topography in posttraumatic stress disorder and non-posttraumatic stress disorder trauma survivors." Addictive Behaviors 26.2 (2001): 247-257.
Source
scival
Published In
Addictive Behaviors
Volume
26
Issue
2
Publish Date
2001
Start Page
247
End Page
257
DOI
10.1016/j.addbeh.2004.05.013

Mecamylamine moderates cue-induced emotional responses in smokers

The nicotinic antagonist, mecamylamine, has been shown to reduce cue-elicited cocaine craving and to aid in smoking cessation. In a within-subjects design, 16 dependent smokers received mecamylamine (10 mg) or placebo capsules on two different days. Subjects imagined smoking urge and non-urge scenarios after smoking their usual brand vs. denicotinized cigarettes. Smoking usual-brand cigarettes produced greater positive effects and mecamylamine blocked heart rate (HR) boost and cigarette sensory impact. Mecamylamine also resulted in greater craving and less calmness, regardless of cigarette smoked. Urge script imagination in the mecamylamine+denicotinized condition resulted in calmness similar to usual-brand conditions and higher than the placebo+denicotinized condition. A similar trend was observed for negative affect. These results suggest that mecamylamine can moderate smoking cue-induced emotional responses in smokers. © 2004 Elsevier Ltd. All rights reserved.

Authors
McClernon, FJ; Rose, JE
MLA Citation
McClernon, FJ, and Rose, JE. "Mecamylamine moderates cue-induced emotional responses in smokers." Addictive Behaviors 26.4 (2001): 741-753.
Source
scival
Published In
Addictive Behaviors
Volume
26
Issue
4
Publish Date
2001
Start Page
741
End Page
753
DOI
10.1016/j.addbeh.2004.08.020

The nicotinic antagonist mecamylamine preferentially inhibits cocaine vs. food self-administration in rats.

Nicotinic acetylcholine systems play important roles in addiction, and nicotinic receptor stimulation stimulates dopamine release while the nicotinic antagonist mecamylamine reduces it. Reid et al. [Neuropsychopharmacology 20 (1999) 297.] recently found in human cocaine addicts that mecamylamine reduced cue-elicited cocaine craving. The current study assessed the impact of mecamylamine on cocaine self-administration in rats. Female Sprague-Dawley rats (N=7) were implanted with intravenous (iv) catheters and trained to lever press for cocaine (0.32 mg/kg/infusion FR-1 with a 60-s timeout) in 45-min sessions. After 2 weeks of training, the rats were injected with saline or mecamylamine (1, 2, or 4 mg/kg sc) 10 min before the session. They received the same dose for 1 week with 1 week of uninjected testing between doses. Mecamylamine, compared to saline, significantly (P<.05) reduced the number of cocaine infusions per session with each of these doses. This effect did not appear to be due to a generalized reduction in behavioral activity. Another set of female Sprague-Dawley rats (N=8) were trained to lever press for food reinforcement. In these rats, the 1 and 2-mg/kg mecamylamine doses had no effect on food self-administration. Significant reductions in food self-administration were not seen unless the high dose of 4-mg/kg mecamylamine was used. Nicotinic antagonist treatment reduces cocaine self-administration in rats at doses that do not cause generalized effects on food-reinforced responding. Nicotinic antagonistic treatment may be a useful new approach to treat cocaine addiction.

Authors
Levin, ED; Mead, T; Rezvani, AH; Rose, JE; Gallivan, C; Gross, R
MLA Citation
Levin, ED, Mead, T, Rezvani, AH, Rose, JE, Gallivan, C, and Gross, R. "The nicotinic antagonist mecamylamine preferentially inhibits cocaine vs. food self-administration in rats." Physiol Behav 71.5 (December 2000): 565-570.
PMID
11239676
Source
pubmed
Published In
Physiology & Behavior
Volume
71
Issue
5
Publish Date
2000
Start Page
565
End Page
570

Dissociating nicotine and nonnicotine components of cigarette smoking.

To dissociate the sensorimotor aspects of cigarette smoking from the pharmacologic effects of nicotine, smokers rated the subjective effects of nicotine-containing or denicotinized cigarettes, and intravenous (IV) nicotine or saline infusions. Three groups of participants (n=20 per group) received either: (1) continuous nicotine, (2) pulsed nicotine, or (3) saline. Each group was exposed to an IV condition once while smoking a denicotinized cigarette and once while not smoking, in a 3x2 mixed design. A fourth group (n=20) received saline while smoking their usual brand of cigarette. The dose and rate of nicotine administration were individualized based on previous measures of ad lib smoke intake. Denicotinized cigarette smoke significantly reduced craving and was rated significantly more satisfying and rewarding than the no-smoking conditions. IV nicotine reduced craving for cigarettes, and increased ratings of lightheadedness and dizziness. However, no significant satisfaction or reward was reported after IV nicotine. The combination of IV nicotine and denicotinized cigarette smoke produced effects similar to those of smoking the usual brand of cigarette. The results suggest that sensorimotor factors are critical in mediating the immediate subjective response to smoking, and that the immediate subjective effects of nicotine administered in doses obtained from cigarette smoking are subtle. Thus, addressing smokers' needs for both for the sensorimotor aspects of smoking as well as for the direct CNS effects of nicotine may be critical in enhancing smoking cessation treatment outcome.

Authors
Rose, JE; Behm, FM; Westman, EC; Johnson, M
MLA Citation
Rose, JE, Behm, FM, Westman, EC, and Johnson, M. "Dissociating nicotine and nonnicotine components of cigarette smoking." Pharmacol Biochem Behav 67.1 (September 2000): 71-81.
PMID
11113486
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
67
Issue
1
Publish Date
2000
Start Page
71
End Page
81

Combining the nicotine inhaler and nicotine patch for smoking cessation

Objective: To assess the combination of the nicotine inhaler and nicotine patch for smoking cessation. Methods: Thirty healthy volunteers were enrolled into this open-label clinical trial of the combined use of nicotine inhalers and patches (15mg/16hr) for 6 weeks, and then nicotine inhalers alone for an additional 6 weeks. Results: Compared to baseline, the percentage salivary cotinine replacement at the end of Week 1 was 74%. One week point abstinence at 6 weeks was 43.3% (95% CL=26%, 61%), and at 12 weeks was 30.0% (95% CL=14%, 46%). Conclusion: The combination of the nicotine inhaler and nicotine patch appears safe and tolerable when used for smoking cessation.

Authors
Westman, EC; Tomlin, KF; Rose, JE
MLA Citation
Westman, EC, Tomlin, KF, and Rose, JE. "Combining the nicotine inhaler and nicotine patch for smoking cessation." American Journal of Health Behavior 24.2 (2000): 114-119.
Source
scival
Published In
American Journal of Health Behavior
Volume
24
Issue
2
Publish Date
2000
Start Page
114
End Page
119

Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction.

An understanding of drug addiction requires knowledge of the effective drug concentrations to which receptors in the nervous system are exposed. It has often been thought that smoking of abused substances such as nicotine or cocaine produces much higher drug concentrations in the arterial blood than those achieved following any other route of administration. However, to date no studies have sampled arterial blood following cigarette smoking with the rapidity necessary to evaluate this hypothesis. We measured arterial plasma nicotine concentrations in samples collected every 5 s from 13 cigarette smokers during cigarette smoking and during administration of nicotine by intravenous injections. Our results show that, for both routes of administration, concentrations of nicotine in arterial blood were more than 10 times lower than expected. Thus, the delivery of nicotine into arterial blood is substantially slower than would be predicted if nicotine were absorbed as rapidly as has generally been assumed. A plausible explanation of these results is that lung uptake of nicotine considerably slows the entry of nicotine into the systemic circulation, as has been shown for other amines. These results have significant implications for theories of addiction to nicotine as well as other drugs such as cocaine that may be subject to binding by lung tissue.

Authors
Rose, JE; Behm, FM; Westman, EC; Coleman, RE
MLA Citation
Rose, JE, Behm, FM, Westman, EC, and Coleman, RE. "Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction." Drug Alcohol Depend 56.2 (September 1, 1999): 99-107.
PMID
10482401
Source
pubmed
Published In
Drug and Alcohol Dependence
Volume
56
Issue
2
Publish Date
1999
Start Page
99
End Page
107

Naltrexone blockade of nicotine effects in cigarette smokers.

RATIONALE: The role of endogenous opiate systems in cigarette smoking remains unclear. In laboratory animals, opiate antagonists block many of the effects of nicotine, but in humans they do not consistently alter smoking behavior. OBJECTIVE: This study explored the effects of naltrexone, alone and in combination with nicotine, on smoking behavior. METHODS: In a double-blind, double-dummy, within-subjects design, 19 regular smokers received four treatments of 1 week duration: naltrexone tablet (50 mg) plus placebo skin patch, placebo tablet plus nicotine skin patch (21 mg/24 h), naltrexone tablet plus nicotine skin patch, and placebo tablet plus placebo skin patch. During each treatment, subjects rated their responses to nicotine-containing and denicotinized cigarettes in the laboratory, and to their own brand of cigarette smoked ad libitum outside the laboratory. RESULTS: Pretreatment with the nicotine patch attenuated smoking-induced decreases in craving, negative affect, and rates of ad lib smoking, and potentiated the aversiveness of a cigarette. Naltrexone reversed these effects of the nicotine patch, and produced negative effects on mood. CONCLUSIONS: The blockade of nicotine's effects by naltrexone supports a role for opioid mechanisms in cigarette smoking.

Authors
Brauer, LH; Behm, FM; Westman, EC; Patel, P; Rose, JE
MLA Citation
Brauer, LH, Behm, FM, Westman, EC, Patel, P, and Rose, JE. "Naltrexone blockade of nicotine effects in cigarette smokers." Psychopharmacology (Berl) 143.4 (April 1999): 339-346.
PMID
10367550
Source
pubmed
Published In
Psychopharmacology
Volume
143
Issue
4
Publish Date
1999
Start Page
339
End Page
346

Blockade of smoking satisfaction using the peripheral nicotinic antagonist trimethaphan.

The present study was conducted to investigate the role of peripheral nicotinic receptors in mediating the rewarding effects of cigarette smoking. Twelve cigarette smokers rated cigarettes after intravenous infusion of the short-acting peripheral nicotinic receptor antagonist trimethaphan and after placebo (saline) infusions. Subjects were blinded to the infusion and cigarette conditions. Cigarette conditions included subjects' usual brand of cigarette, denicotinized tobacco cigarettes, and nicotine-injected cigarettes that had a tar delivery equal to that of the denicotinized cigarettes but with an enhanced nicotine delivery equal to that of subjects' usual brands. The latter cigarettes were rated as extremely harsh due to the high nicotine/tar ratio. Trimethaphan significantly attenuated the airway sensations associated with nicotine, and eliminated the difference in smoking satisfaction between the usual brand of cigarette and the other two cigarettes. These findings suggest that nicotinic receptors on peripheral nerve endings in the respiratory tract modulate smoking satisfaction and may be important in the maintenance of cigarette addiction.

Authors
Rose, JE; Westman, EC; Behm, FM; Johnson, MP; Goldberg, JS
MLA Citation
Rose, JE, Westman, EC, Behm, FM, Johnson, MP, and Goldberg, JS. "Blockade of smoking satisfaction using the peripheral nicotinic antagonist trimethaphan." Pharmacol Biochem Behav 62.1 (January 1999): 165-172.
PMID
9972860
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
62
Issue
1
Publish Date
1999
Start Page
165
End Page
172

Transdermal nicotine effects on attention.

Nicotine has been shown to improve attentiveness in smokers and attenuate attentional deficits in Alzheimer's disease patients, schizophrenics and adults with attention-deficit/hyperactivity disorder (ADHD). The current study was conducted to determine whether nicotine administered via transdermal patches would improve attentiveness in non-smoking adults without attentional deficits. The subjects underwent the nicotine and placebo exposure in a counterbalanced double-blind manner. Measures of treatment effect included the Profile of Mood States (POMS), Conners' computerized Continuous Performance Test (CPT) of attentiveness and a computerized interval-timing task. The subjects were administered a 7 mg/day nicotine transdermal patch for 4.5 h during a morning session. Nicotine significantly increased self-perceived vigor as measured by the POMS test. On the CPT, nicotine significantly decreased the number of errors of omission without causing increases in either errors of commission or correct hit reaction time. Nicotine also significantly decreased the variance of hit reaction time and the composite measure of attentiveness. This study shows that, in addition to reducing attentional impairment, nicotine administered via transdermal patches can improve attentiveness in normal adult non-smokers.

Authors
Levin, ED; Conners, CK; Silva, D; Hinton, SC; Meck, WH; March, J; Rose, JE
MLA Citation
Levin, ED, Conners, CK, Silva, D, Hinton, SC, Meck, WH, March, J, and Rose, JE. "Transdermal nicotine effects on attention." Psychopharmacology (Berl) 140.2 (November 1998): 135-141.
PMID
9860103
Source
pubmed
Published In
Psychopharmacology
Volume
140
Issue
2
Publish Date
1998
Start Page
135
End Page
141

Nicotine-mecamylamine treatment for smoking cessation: the role of pre-cessation therapy.

The nicotinic antagonist mecamylamine was evaluated in a randomized smoking cessation trial. Four groups of participants (n = 20 per group) received nicotine plus mecamylamine, nicotine alone, mecamylamine alone, or no drug for 4 weeks before cessation. After the quit-smoking date, all subjects received nicotine plus mecamylamine treatment for 6 weeks. Nicotine skin patches (21 mg/24 hr) and mecamylamine capsules (2.5-5.0 mg twice per day) were used. Precessation mecamylamine significantly prolonged the duration of continuous smoking abstinence; abstinence rates at the end of treatment were 47.5% with mecamylamine and 27.5% without mecamylamine. Nicotine + mecamylamine reduced ad lib smoking, smoking satisfaction, and craving more than either drug alone. Moreover, the orthostatic decrease in blood pressure caused by mecamylamine was offset by nicotine. Mecamylamine before smoking cessation may be an effective adjunct to nicotine patch therapy.

Authors
Rose, JE; Behm, FM; Westman, EC
MLA Citation
Rose, JE, Behm, FM, and Westman, EC. "Nicotine-mecamylamine treatment for smoking cessation: the role of pre-cessation therapy." Exp Clin Psychopharmacol 6.3 (August 1998): 331-343.
PMID
9725117
Source
pubmed
Published In
Experimental and Clinical Psychopharmacology
Volume
6
Issue
3
Publish Date
1998
Start Page
331
End Page
343

Conference on tobacco dependence: Innovative regulatory approaches to reduce death and disease: Selected excerpts from conference proceedings

Authors
Dretchen, KL; Slade, J; Kessler, DA; Koop, CE; Burns, DM; Safir, PO; Henningfield, JE; Peck, CC; Page, JA; Zeller, MR; al, E
MLA Citation
Dretchen, KL, Slade, J, Kessler, DA, Koop, CE, Burns, DM, Safir, PO, Henningfield, JE, Peck, CC, Page, JA, Zeller, MR, and al, E. "Conference on tobacco dependence: Innovative regulatory approaches to reduce death and disease: Selected excerpts from conference proceedings." Food and Drug Law Journal 53.SUPPL. (1998): 115-137.
Source
scival
Published In
Food and drug law journal
Volume
53
Issue
SUPPL.
Publish Date
1998
Start Page
115
End Page
137

Membership of tobacco industry scientists in scientific societies.

Authors
Perkins, KA
MLA Citation
Perkins, KA. "Membership of tobacco industry scientists in scientific societies." Addiction (Abingdon, England) 92.5 (May 1997): 517-520.
PMID
9219375
Source
epmc
Published In
Addiction
Volume
92
Issue
5
Publish Date
1997
Start Page
517
End Page
520
DOI
10.1080/09652149737782

Nicotine self-administration in animals and humans: similarities and differences.

Studies of nicotine self-administration in animal and human subjects are discussed with respect to the behavioral paradigms employed, the effects of nicotine dose manipulations and nicotinic agonist/antagonist pretreatment, and the role of neurochemical processes mediating reinforcement. Animal models have focused on intravenous nicotine self-administration, while most studies in human subjects have studied cigarette smoking behavior. Despite procedural differences, data from both animal and human studies show an inverted-U function relating nicotine dose to self-administration behavior, with maximal rates of responding occurring at intermediate doses of nicotine. Moreover, nicotine supplementation via non-contingent nicotine administration suppresses nicotine self-administration behavior in both animal models and human cigarette smokers. Nicotine antagonist treatment also reduces responding, although human studies usually find a transient increase in smoking, which is interpreted as an attempt to compensate for nicotinic receptor blockade. Amongst the neurochemical systems which have been examined, most emphasis has been given to dopamine. The mesolimbic dopamine pathway has been implicated in nicotine reward based on animal studies, and research with humans suggests a role for dopaminergic processes as well. However, dopaminergic blockade appears to increase cigarette smoking behavior in humans, while in animals nicotine self-administration is attenuated. Future research should exploit the complementary aspects of animal models and human paradigms to provide a coherent understanding of nicotine reinforcement. Animal models allow for analysis of anatomical and physiological mechanisms underlying nicotine self-administration; human studies validate the relevance to tobacco dependence and smoking cessation treatment.

Authors
Rose, JE; Corrigall, WA
MLA Citation
Rose, JE, and Corrigall, WA. "Nicotine self-administration in animals and humans: similarities and differences." Psychopharmacology (Berl) 130.1 (March 1997): 28-40. (Review)
PMID
9089846
Source
pubmed
Published In
Psychopharmacology
Volume
130
Issue
1
Publish Date
1997
Start Page
28
End Page
40

Smoking behavior on the first day of a quit attempt predicts long-term abstinence.

BACKGROUND: The nicotine patch has been widely used for smoking cessation, but not all smokers quit using the patch. Knowing which smokers are likely to succeed with the nicotine patch may improve the efficiency of nicotine patch use. OBJECTIVE: To identify predictors of smoking abstinence using baseline characteristics, smoking behavior, and withdrawal symptoms. METHODS: Using 2 randomized clinical trials of pharmacologic treatment, brief counseling, and quit date formats in the outpatient research clinic setting, predictors of smoking cessation were derived in 1 sample (n = 159), then prospectively validated in an independent sample (n = 48). Subjects smoked 1 pack of cigarettes per day or more and were motivated to quit smoking. Self-report of abstinence at 6 months verified by exhaled carbon monoxide of 8 ppm or less was used. RESULTS: Abstinence at 6 months was 24% in the derivation set and 25% in the validation set. Using logistic regression, a model containing quit date abstinence (odds ratio, 10.6; 95% confidence interval [CI], 2.9-38.7) and baseline nicotine dependence (odds ratio, 0.75; 95% CI, 0.6-1.0 per unit increase in Fagerstrom score) provided the optimal predictive ability and was validated in the independent set. Quit date abstinence improved the likelihood of 6-month abstinence by 4.1 over baseline (95% CI, 2.6-6.4) for low-nicotine-dependent smokers and 1.2 (95% CI, 0.6-2.2) for high-nicotine-dependent smokers. Quit date smoking altered the likelihood of 6-month abstinence by 0.2 (95% CI, 0.0-0.8) for low-dependent smokers and 0.1 for high-dependent smokers (95% CI, 0.0-0.6). CONCLUSIONS: Abstinence on the quit date and low-nicotine dependence improve the likelihood of smoking abstinence at 6 months. Smoking on the quit date may be an indication for postponing the cessation attempt or adjusting the therapy for smoking cessation.

Authors
Westman, EC; Behm, FM; Simel, DL; Rose, JE
MLA Citation
Westman, EC, Behm, FM, Simel, DL, and Rose, JE. "Smoking behavior on the first day of a quit attempt predicts long-term abstinence." Arch Intern Med 157.3 (February 10, 1997): 335-340.
PMID
9040302
Source
pubmed
Published In
Archives of internal medicine
Volume
157
Issue
3
Publish Date
1997
Start Page
335
End Page
340

Nicotine-haloperidol interactions and cognitive performance in schizophrenics.

Nearly 90% of schizophrenics smoke cigarettes, considerably higher than the general population's rate of 25%. There is some indication that schizophrenics may smoke as a form of self-medication. Nicotine has a variety of pharmacologic effects that may both counteract some of the cognitive deficits of schizophrenia and counteract some of the adverse side effects of antipsychotic drugs. In the current study, we assessed the interactions of haloperidol and nicotine on cognitive performance of a group of schizophrenics. These patients were in a double-blind study, randomly assigning them to low, moderate, and high dose levels of haloperidol. The subjects, all smokers, came to the laboratory on four different mornings after overnight deprivation from cigarettes. In a double-blind fashion, they were administered placebo, low (7 mg/day), medium (14 mg/day), or high (21 mg/day) dose nicotine skin patches. Three hours after administration of the skin patch, the subjects were given a computerized cognitive test battery including: simple reaction time, complex reaction time (spatial rotation), delayed matching to sample, the Sternberg memory test, and the Conners continuous performance test (CPT). With the placebo nicotine patch, there was a haloperidol dose-related impairment in delayed matching to sample choice accuracy and an increase in response time on the complex reaction time task. Nicotine caused a dose-related reversal of the haloperidol-induced impairments in memory performance and complex reaction time. In the CPT, nicotine reduced the variability in response that is associated with attentional deficit. These results demonstrate the effects of nicotine in reversing some of the adverse side effects of haloperidol and improving cognitive performance in schizophrenia.

Authors
Levin, ED; Wilson, W; Rose, JE; McEvoy, J
MLA Citation
Levin, ED, Wilson, W, Rose, JE, and McEvoy, J. "Nicotine-haloperidol interactions and cognitive performance in schizophrenics." Neuropsychopharmacology 15.5 (November 1996): 429-436.
PMID
8914115
Source
pubmed
Published In
Neuropsychopharmacology (Nature)
Volume
15
Issue
5
Publish Date
1996
Start Page
429
End Page
436
DOI
10.1016/S0893-133X(96)00018-8

Quitting smoking raises whole blood glutathione.

Cigarette smoke contains numerous oxygen free radicals that may be important in smoking-related disease pathogenesis. These free radicals may overwhelm antioxidant defenses and produce a condition of oxidative stress that can result in damage to DNA and other cellular components. This study investigated whether or not indications of harmful oxidative stress decline following smoking cessation. Changes in whole blood glutathione (GSH), an index of oxidative stress level, were determined for 30 cigarette smokers who participated in an experimental smoking-cessation program. Measurements were taken during ad lib smoking and 3 weeks after smoking cessation. In 22 individuals who were continuously abstinent for 3 weeks, GSH levels rose significantly following smoking cessation, from 5.0 to 6.1 mumol/g Hb (p < 0.001). Individuals with the lowest GSH levels during ad lib smoking showed the greatest increases following cessation. Results suggest that oxidative stress and free-radical damage diminish soon after smoking cessation. Thus, some significant health benefits may appear rapidly when people quit smoking.

Authors
Lane, JD; Opara, EC; Rose, JE; Behm, F
MLA Citation
Lane, JD, Opara, EC, Rose, JE, and Behm, F. "Quitting smoking raises whole blood glutathione." Physiol Behav 60.5 (November 1996): 1379-1381.
PMID
8916198
Source
pubmed
Published In
Physiology & Behavior
Volume
60
Issue
5
Publish Date
1996
Start Page
1379
End Page
1381

Do heavy smokers need a higher replacement dose of nicotine to quit?

Authors
Westman, EC; Rose, JE
MLA Citation
Westman, EC, and Rose, JE. "Do heavy smokers need a higher replacement dose of nicotine to quit?." JAMA 275.24 (June 26, 1996): 1882-1883. (Letter)
PMID
8648863
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
275
Issue
24
Publish Date
1996
Start Page
1882
End Page
1883

Dissociating the nicotine and airway sensory effects of smoking.

This study examined the subjective and cardiovascular effects of two of the components of cigarette smoking when given separately: nicotine and airway sensations. Using a within-subjects design, six healthy volunteer smokers, age 18-45 years, who smoked at least 20 cigarettes per day were given six conditions in a randomized, counterbalanced order. The effects of IV nicotine, IV saline, and denicotinized cigarettes were compared to a standard 1-mg cigarette. The standard cigarette produced more of a calming effect and more irritability reduction than either the nicotine or airway sensations alone. The denicotinized cigarette was similar to the standard cigarette condition, except the cigarette condition was associated with higher feelings of "exhilaration." Many of the positive subjective effects from a denicotinized cigarette were comparable to that of a standard cigarette. These data support the hypothesis that replacement of the sensory cues of smoking with "airway sensory replacement" may be useful for smoking cessation.

Authors
Westman, EC; Behm, FM; Rose, JE
MLA Citation
Westman, EC, Behm, FM, and Rose, JE. "Dissociating the nicotine and airway sensory effects of smoking." Pharmacol Biochem Behav 53.2 (February 1996): 309-315.
PMID
8808137
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
53
Issue
2
Publish Date
1996
Start Page
309
End Page
315

Nicotine effects on adults with attention-deficit/hyperactivity disorder.

Several lines of evidence suggest that nicotine may be useful in treating the symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). The current study was an acute, placebo-controlled double-blind experiment to determine whether nicotine might be useful as an alternative treatment of adults with ADHD symptomatology. Six smokers and 11 nonsmokers who were outpatient referrals for ADHD were diagnosed by DSM-IV criteria. Measures of treatment effect included the Clinical Global Impressions (CGI) scale, Hopkins' symptom check list (SCL-90-R), the Profile of Mood States (POMS), Conners' computerized Continuous Performance Test (CPT), the Stroop test, and an interval-timing task. The smokers underwent overnight deprivation from smoking and were given a 21 mg/day nicotine skin patch for 4.5 h during a morning session. The nonsmokers were given a 7 mg/day nicotine skin patch for 4.5 h during a morning session. Active and placebo patches were given in a counter-balanced order approximately 1 week apart. Nicotine caused a significant overall nicotine-induced improvement on the CGI. This effect was significant when only the nonsmokers were considered, which indicated that it was not due merely to withdrawal relief. Nicotine caused significantly increased vigor as measured by the POMS test. Nicotine caused an overall significant reduction in reaction time (RT) on the CPT, as well as, with the smokers, a significant reduction in another index of inattention, variability in reaction time over trial blocks. Nicotine improved accuracy of time estimation and lowered variability of time-estimation response curves. Because improvements occurred among nonsmokers, the nicotine effect appears not to be merely a relief of withdrawal symptoms. It is concluded that nicotine deserves further clinical trials with ADHD.

Authors
Levin, ED; Conners, CK; Sparrow, E; Hinton, SC; Erhardt, D; Meck, WH; Rose, JE; March, J
MLA Citation
Levin, ED, Conners, CK, Sparrow, E, Hinton, SC, Erhardt, D, Meck, WH, Rose, JE, and March, J. "Nicotine effects on adults with attention-deficit/hyperactivity disorder." Psychopharmacology (Berl) 123.1 (January 1996): 55-63.
PMID
8741955
Source
pubmed
Published In
Psychopharmacology
Volume
123
Issue
1
Publish Date
1996
Start Page
55
End Page
63
DOI
10.1007/BF02246281

Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD).

Nicotine, like the psychostimulants methylphenidate and dextroamphetamine, acts as an indirect dopamine agonist and improves attention and arousal. Adults and adolescents with attention deficit hyperactivity disorder (ADHD) smoke much more frequently than normal individuals or those with other psychiatric conditions, perhaps as a form of self-medication for ADHD symptoms. Nicotine might therefore have some value as a treatment for ADHD. The present study is an acute double-blind crossover administration of nicotine and placebo with smokers (n = 6) and nonsmokers (n = 11) diagnosed with adult ADHD. The drug was delivered via a transdermal patch at a dosage of 7 mg/day for nonsmokers and 21 mg/day for smokers. Results indicate significant clinician-rated global improvement, self-rated vigor and concentration, and improved performance on chronometric measures of attention and timing accuracy. Side effects were minimal. These acute results indicate the need for a longer clinical trial and a comparison with other stimulants in adult ADHD treatment.

Authors
Conners, CK; Levin, ED; Sparrow, E; Hinton, SC; Erhardt, D; Meck, WH; Rose, JE; March, J
MLA Citation
Conners, CK, Levin, ED, Sparrow, E, Hinton, SC, Erhardt, D, Meck, WH, Rose, JE, and March, J. "Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD)." Psychopharmacol Bull 32.1 (1996): 67-73.
PMID
8927677
Source
pubmed
Published In
Psychopharmacology bulletin
Volume
32
Issue
1
Publish Date
1996
Start Page
67
End Page
73

Nicotine and neurobehavioral function

Authors
Levin, ED; Rose, JE; Lippelio, P; Robinson, J
MLA Citation
Levin, ED, Rose, JE, Lippelio, P, and Robinson, J. "Nicotine and neurobehavioral function." Drug Development Research 38.3-4 (1996): 135--.
Source
scival
Published In
Drug Development Research
Volume
38
Issue
3-4
Publish Date
1996
Start Page
135-
DOI
10.1002/(SICI)1098-2299(199607/08)38:3/4<135::AID-DDR1>3.0.CO;2-N

Airway sensory replacement as a treatment for smoking cessation

Although nicotine may be a necessary component of the smoking addiction, it is obvious even to the non-expert that there is far more to smoking than the delivery of nicotine alone. Among the many aspects of smoking that smokers find pleasurable, 60% of smokers report liking of the feeling of cigarette smoke in the throat and chest. This paper summarizes several studies that strongly suggest that the airway sensations of smoking are important for at least the short-term satisfaction and craving reduction of cigarette smoking, and that these sensations can be reproduced by several other substances than cigarette smoke. Airway sensory replacement, especially in combination with nicotine replacement, may fill one of the many gaps that currently exist in smoking cessation treatment.

Authors
Westman, EC; Behm, FM; Rose, JE
MLA Citation
Westman, EC, Behm, FM, and Rose, JE. "Airway sensory replacement as a treatment for smoking cessation." Drug Development Research 38.3-4 (1996): 257-262.
Source
scival
Published In
Drug Development Research
Volume
38
Issue
3-4
Publish Date
1996
Start Page
257
End Page
262
DOI
10.1002/(SICI)1098-2299(199607/08)38:3/4<257::AID-DDR14>3.0.CO;2-W

Nicotine/mecamylamine combination treatment for smoking cessation

Pharmacotherapies for smoking cessation that can be used in a minimal behavioral intervention setting are urgently needed. The studies described in this article show that the nicotinic antagonist mecamylamine is efficacious when administered in combination with nicotine replacement. Mecamylamine and nicotine have been shown to act in concert to attenuate the rewarding effects of cigarette smoking, reduce craving, and suppress ad lib smoking. Moreover, long-term abstinence rates following nicotine/mecamylamine treatment are roughly two to three times higher than with standard nicotine replacement therapy using nicotine skin patches. In one study, the initiation of mecamylamine treatment prior to the target quit-smoking date was shown to be critical in promoting subsequent continuous abstinence from smoking. The main interpretation of this finding is that smoking in the presence of blockade of reward promotes extinction of smoking behavior, raising the likelihood of successful smoking cessation. Directions for future research are also discussed, including mechanistic studies of nicotinic receptor subtypes affected by nicotine and mecamylamine, as well as assessment of the optimal timing, doses, and route of administration of the two drugs in smoking cessation treatment. Overall, the results show that two classic approaches to the treatment of drug dependence, substitution, and blockade, are not mutually exclusive and in fact can be combined fruitfully in the treatment of nicotine addiction.

Authors
Rose, JE; Westman, EC; Behm, FM
MLA Citation
Rose, JE, Westman, EC, and Behm, FM. "Nicotine/mecamylamine combination treatment for smoking cessation." Drug Development Research 38.3-4 (1996): 243-256.
Source
scival
Published In
Drug Development Research
Volume
38
Issue
3-4
Publish Date
1996
Start Page
243
End Page
256
DOI
10.1002/(SICI)1098-2299(199607/08)38:3/4<243::AID-DDR13>3.0.CO;2-#

Nicotine addiction and treatment.

The persistence of cigarette smoking despite widespread awareness of adverse health effects results from an underlying addiction to nicotine. Unaided attempts to quit smoking are generally unsuccessful. This article discusses nicotine addition and therapeutic techniques that have been or are being developed to relieve smoking withdrawal symptoms and promote abstinence from smoking. These techniques include nicotine chewing gum, skin patches, nasal sprays, and inhalers, as well as pharmacotherapies such as mecamylamine and clonidine, serotonergic treatments such as buspirone, and antidepressants such as buproprion. A nondrug approach using cigarette substitutes that mimic the airway sensations produced by cigarette smoke is also discussed.

Authors
Rose, JE
MLA Citation
Rose, JE. "Nicotine addiction and treatment." Annu Rev Med 47 (1996): 493-507. (Review)
PMID
8712799
Source
pubmed
Published In
Annual Review of Medicine
Volume
47
Publish Date
1996
Start Page
493
End Page
507
DOI
10.1146/annurev.med.47.1.493

Smoking in Vietnam combat veterans with post-traumatic stress disorder.

The present study investigated smoking prevalence, smoking motives, demographic variables and psychological symptoms in 124 help-seeking, male Vietnam combat veterans with post-traumatic stress disorder (PTSD). A high percentage of these veterans smoked (60%). Vietnam veterans with PTSD who smoked were more likely than those who did not smoke to report higher levels of PTSD symptoms, depression and trait anxiety. Increased depression was associated with increased automatic smoking. Smokers reported a high frequency of smoking in response to military memories. Implications for smoking interventions, cessation, and relapse prevention efforts are discussed.

Authors
Beckham, JC; Roodman, AA; Shipley, RH; Hertzberg, MA; Cunha, GH; Kudler, HS; Levin, ED; Rose, JE; Fairbank, JA
MLA Citation
Beckham, JC, Roodman, AA, Shipley, RH, Hertzberg, MA, Cunha, GH, Kudler, HS, Levin, ED, Rose, JE, and Fairbank, JA. "Smoking in Vietnam combat veterans with post-traumatic stress disorder." J Trauma Stress 8.3 (July 1995): 461-472.
PMID
7582610
Source
pubmed
Published In
Journal of Traumatic Stress
Volume
8
Issue
3
Publish Date
1995
Start Page
461
End Page
472

Effects of nicotinic dimethylaminoethyl esters on working memory performance of rats in the radial-arm maze.

Nicotine has been found to improve memory performance in a variety of tests, including the radial-arm maze. This improvement, together with the consistent finding of a decline in cortical nicotinic receptor concentration in Alzheimer's patients, has fueled the search for novel nicotinic ligands with therapeutic potential. In the current studies, a series of nicotinic compounds was tested for effects on working memory performance in the radial-arm maze. One of the three compounds tested, DMAE II (dimethylaminoethanol cyclohexyl carboxylate fumurate), produced significant improvements in working memory performance. In the first experiment, this drug produced a biphasic dose-response curve with improved performance at the 20-mg/kg dose but not at 10 or 40 mg/kg. In a second round of DMAE II administration, the same rats showed a significant improvement with the 40-mg/kg dose. In the second experiment, a new set of rats also showed a biphasic dose-response to DMAE II. The 20-mg/kg dose caused a significant improvement whereas the 40-mg/kg dose did not. Interactions of DMAE II with nicotine and mecamylamine were also studied. Nicotine (0.2 mg/kg) by itself caused a significant improvement in working memory performance. No additive effects of DMAE II with nicotine were seen. In fact, some attenuation of response was seen with the combination. Choice accuracy data for mecamylamine could not be analyzed because of excessive sedation and nonresponding. These studies show that, like nicotine, the nicotinic ligand DMAE II causes an improvement in radial-arm mace choice accuracy. The lack of additivity with nicotine may have been to the partial agonist effects of DMAE II.

Authors
Levin, ED; Rose, JE; Abood, L
MLA Citation
Levin, ED, Rose, JE, and Abood, L. "Effects of nicotinic dimethylaminoethyl esters on working memory performance of rats in the radial-arm maze." Pharmacol Biochem Behav 51.2-3 (June 1995): 369-373.
PMID
7667355
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
51
Issue
2-3
Publish Date
1995
Start Page
369
End Page
373

Acute and chronic nicotinic interactions with dopamine systems and working memory performance.

Nicotine has been found to improve memory performance in a variety of tests in rats, monkeys, and humans. Interactions of nicotinic systems with dopamine (DA) systems may be important for this effect. We conducted a series of studies of nicotinic agonist and antagonist interactions with DA systems using rats in a win-shift working memory task in the radial-arm maze. The working memory deficit caused by the nicotinic antagonist mecamylamine was potentiated by the D1/D2 DA antagonist haloperidol and the specific D2 antagonist raclopride. In contrast, the mecamylamine-induced deficit was reversed by co-administration of the D2/D3 agonist quinpirole. Nicotine also has significant interactions with dopamine drugs with regard to working memory performance in the radial-arm maze. The DA agonist pergolide did not by itself improve radial-arm maze memory performance, but when given together with nicotine it produced an elevated dose-dependent increase in choice accuracy. The D1 agonist SKF 38393 significantly impaired radial-arm maze choice accuracy. Nicotine was effective in reversing this deficit. When given together with nicotine, the D2/D3 agonist quinpirole improved RAM choice accuracy relative to either drug alone. Acute local infusion of mecamylamine to the midbrain DA nuclei effectively impairs working memory function in the radial-arm maze. In contrast to acute nicotinic manipulations, considerably less evidence exists that the effects of chronic nicotine administration are influenced by DA systems. This may be an example of the different neural substrates that underlie the memory improvement caused by acute and chronic nicotine.

Authors
Levin, ED; Rose, JE
MLA Citation
Levin, ED, and Rose, JE. "Acute and chronic nicotinic interactions with dopamine systems and working memory performance." Ann N Y Acad Sci 757 (May 10, 1995): 245-252. (Review)
PMID
7611680
Source
pubmed
Published In
Annals of the New York Academy of Sciences
Volume
757
Publish Date
1995
Start Page
245
End Page
252

Combined administration of agonist-antagonist as a method of regulating receptor activation.

Authors
Rose, JE; Levin, ED; Behm, FM; Westman, EC; Stein, RM; Lane, JD; Ripka, GV
MLA Citation
Rose, JE, Levin, ED, Behm, FM, Westman, EC, Stein, RM, Lane, JD, and Ripka, GV. "Combined administration of agonist-antagonist as a method of regulating receptor activation." Ann N Y Acad Sci 757 (May 10, 1995): 218-221.
PMID
7611676
Source
pubmed
Published In
Annals of the New York Academy of Sciences
Volume
757
Publish Date
1995
Start Page
218
End Page
221

Haloperidol increases smoking in patients with schizophrenia.

Ten patients with schizophrenia participated in 120-min free-smoking sessions when actively psychotic and free of antipsychotic medications, and again after the initiation of haloperidol treatment. During these free-smoking sessions they had access to cigarettes ad libitum. Their expired air carbon monoxide (CO) and plasma nicotine and cotinine levels were measured at the end of the 120-min free-smoking sessions. These patients smoked more after starting haloperidol treatment, relative to their baseline rate of smoking when free of antipsychotic medications, as evidenced by significantly higher expired CO and plasma nicotine levels.

Authors
McEvoy, JP; Freudenreich, O; Levin, ED; Rose, JE
MLA Citation
McEvoy, JP, Freudenreich, O, Levin, ED, and Rose, JE. "Haloperidol increases smoking in patients with schizophrenia." Psychopharmacology (Berl) 119.1 (May 1995): 124-126.
PMID
7675943
Source
pubmed
Published In
Psychopharmacology
Volume
119
Issue
1
Publish Date
1995
Start Page
124
End Page
126

Airway sensory replacement combined with nicotine replacement for smoking cessation. A randomized, placebo-controlled trial using a citric acid inhaler.

STUDY OBJECTIVE: This study was conducted to determine if the combination of airway sensory replacement and nicotine replacement improves 10-week smoking abstinence rates over nicotine replacement alone. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Outpatient research clinic. PARTICIPANTS: One hundred healthy volunteers who smoked at least one pack of cigarettes per day and desired to quit smoking. INTERVENTIONS: Subjects received either citric acid (n = 41) or lactose placebo (n = 59) inhalers to cope with smoking urges for 10 weeks. All subjects received self-help materials and nicotine patches for 6 weeks. Return visits were at weeks 1, 4, 6, and 10. Abstinence was defined as zero cigarettes smoked since the quit date verified by exhaled carbon monoxide < or = 8 ppm at all return visits. Inhaler effects were measured by a standardized questionnaire. MEASUREMENTS AND RESULTS: The primary outcome of continuous abstinence at the end of the 10-week treatment period was 19.5% (95% confidence interval [CI] = 7.4 to 31.6%) for the citric acid group vs 6.8% (95% CI = 0.4 to 13.2%) for the lactose group (p = 0.05). Relief from craving and short-term abstinence increased as airway sensations from the inhaler also increased. Abstinence at 10 weeks for subjects receiving strong airway sensations from the inhalers was 33.3% (95% CI = 14.5 to 52.1%). At 6 months, there was no difference in abstinence between the treatment groups (0% vs 5.1%, p = 0.20). CONCLUSIONS: When combined with the nicotine patch, the citric acid inhaler improved 10-week smoking abstinence over lactose inhaler. The combination of airway sensory replacement and nicotine replacement may prove beneficial for smoking cessation.

Authors
Westman, EC; Behm, FM; Rose, JE
MLA Citation
Westman, EC, Behm, FM, and Rose, JE. "Airway sensory replacement combined with nicotine replacement for smoking cessation. A randomized, placebo-controlled trial using a citric acid inhaler." Chest 107.5 (May 1995): 1358-1364.
PMID
7750331
Source
pubmed
Published In
Chest
Volume
107
Issue
5
Publish Date
1995
Start Page
1358
End Page
1364

Nicotine as a therapeutic drug.

Current evidence about the therapeutic potential of nicotine is strongest for ulcerative colitis. The role, if any, of nicotine therapy in Parkinson's or Alzheimer's diseases is not clear, but further research appears warranted. We need more information about the tolerability and safety of nicotine administration in such diseases. At present, any therapeutic trials of nicotine therapy should occur only as part of research protocols. Further nonjudgmental examination of the perceived effects of tobacco use may lead to other uses of nicotine. However, given the widespread morbidity and mortality directly attributable to tobacco use, no form of tobacco should be used to deliver nicotine. We encourage everyone who uses tobacco products to quit.

Authors
Westman, EC; Levin, ED; Rose, JE
MLA Citation
Westman, EC, Levin, ED, and Rose, JE. "Nicotine as a therapeutic drug." N C Med J 56.1 (January 1995): 48-51. (Review)
PMID
7862206
Source
pubmed
Published In
North Carolina Medical Journal
Volume
56
Issue
1
Publish Date
1995
Start Page
48
End Page
51

Effects of Cigarette Smoking on Perception of Thermal Pain

The effects of cigarette smoking on pain perception were evaluated in 18 healthy smokers. Thermal pain stimuli were used to assess pain detection threshold and tolerance and to collect subjective ratings of the intensity and unpleasantness of painful stimuli. After overnight abstinence, pain perception was evaluated before and after 3 experimental treatments. Participants smoked normal cigarettes, smoked denicotinized cigarettes, or remained abstinent. Smoking normal cigarettes produced relative increases in pain tolerance compared with abstinence. Smoking denicotinized cigarettes produced intermediate effects on tolerance not different from the other 2 treatments. Effects were not detected for pain threshold or subjective pain ratings. Results suggest that cigarette smoking can have antinociceptive effects, which may depend both on nicotine and on other factors associated with smoking. © 1995 American Psychological Association.

Authors
Lane, JD; Lefebvre, JC; Rose, JE; Keefe, FJ
MLA Citation
Lane, JD, Lefebvre, JC, Rose, JE, and Keefe, FJ. "Effects of Cigarette Smoking on Perception of Thermal Pain." Experimental and Clinical Psychopharmacology 3.2 (1995): 140-147.
Source
scival
Published In
Experimental and Clinical Psychopharmacology
Volume
3
Issue
2
Publish Date
1995
Start Page
140
End Page
147

Effects of Daily Caffeine Intake on Smoking Behavior in the Natural Environment

The effects of changes in daily caffeine intake on cigarette smoking were investigated. Forty cigarette smokers consumed caffeine ad lib on a baseline day then consumed controlled multiple doses of caffeine (100 mg and 500 mg per day) for two-day trials. Smokers recorded the number of cigarettes consumed, and measurements of expired-air carbon monoxide and salivary cotinine concentration were obtained to estimate smoke and nicotine intake. Baseline caffeine intake averaged 449 mg per day, with wide variations among participants. The 5-fold change in caffeine dose on treatment days did not affect any measure of smoking behavior in these participants. Results suggest that daily caffeine intake has little influence on cigarette smoking in the natural environment. Coffee drinking and cigarette smoking are commonly associated behaviors, although the links between them are not yet understood. Results raise doubts that the influence of coffee drinking on smoking, if any, can be attributed to the effects of caffeine. © 1995 American Psychological Association.

Authors
Lane, JD; Rose, JE
MLA Citation
Lane, JD, and Rose, JE. "Effects of Daily Caffeine Intake on Smoking Behavior in the Natural Environment." Experimental and Clinical Psychopharmacology 3.1 (1995): 49-55.
Source
scival
Published In
Experimental and Clinical Psychopharmacology
Volume
3
Issue
1
Publish Date
1995
Start Page
49
End Page
55

Clozapine decreases smoking in patients with chronic schizophrenia

Authors
McEvoy, J; Freudenreich, O; McGee, M; Vanderzwaag, C; Levin, E; Rose, J
MLA Citation
McEvoy, J, Freudenreich, O, McGee, M, Vanderzwaag, C, Levin, E, and Rose, J. "Clozapine decreases smoking in patients with chronic schizophrenia." Biological Psychiatry 37.8 (1995): 550-552.
PMID
7619979
Source
scival
Published In
Biological Psychiatry
Volume
37
Issue
8
Publish Date
1995
Start Page
550
End Page
552
DOI
10.1016/0006-3223(94)00365-A

Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone.

OBJECTIVE: To evaluate concurrent administration of mecamylamine (nicotine antagonist) with nicotine skin patch treatment for smoking cessation. METHODS: This was a randomized, double-blind, placebo-controlled trial. Forty-eight healthy smokers who smoked at least one pack per day were studied at an outpatient smoking cessation research clinic. The subjects ranged in age from 20 to 40 years. Intervention with the nicotine skin patch (6 to 8 weeks) plus oral mecamylamine (2.5 to 5 mg twice a day for 5 weeks) was compared to nicotine patch plus placebo. Mecamylamine treatment began 2 weeks before smoking cessation. The primary outcome was continuous abstinence through 7 weeks after cessation (1 week after treatment), confirmed by expired air carbon monoxide measurements. Secondary measures included point abstinence at 7 weeks, continuous abstinence at 6- and 12-month follow-up, and self-reported withdrawal symptoms. RESULTS: The continuous abstinence rate at 7 weeks was three times higher in the mecamylamine condition: 50% versus 16.7%, p = 0.015. Point abstinence at 7 weeks was 58% for mecamylamine versus 29% for placebo, p = 0.044. At follow-up, continuous abstinence remained higher for mecamylamine: 37.5% versus 12.5% at 6 months (p = 0.046) and 37.5% versus 4.2% at 12 months (p = 0.004). Mecamylamine also significantly reduced craving for cigarettes, negative affect, and appetite. CONCLUSIONS: Agonist-antagonist therapy, consisting of the nicotine patch with oral mecamylamine, may substantially improve current smoking cessation treatment.

Authors
Rose, JE; Behm, FM; Westman, EC; Levin, ED; Stein, RM; Ripka, GV
MLA Citation
Rose, JE, Behm, FM, Westman, EC, Levin, ED, Stein, RM, and Ripka, GV. "Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone." Clin Pharmacol Ther 56.1 (July 1994): 86-99.
PMID
8033499
Source
pubmed
Published In
Clinical Pharmacology & Therapeutics (Nature)
Volume
56
Issue
1
Publish Date
1994
Start Page
86
End Page
99

Nicotine skin patch treatment increases abstinence, decreases withdrawal symptoms, and attenuates rewarding effects of smoking.

A variety of studies have shown that nicotine skin patches are effective in promoting smoking cessation. This study replicated this effect, in addition, nicotine skin patches were found to decrease a variety of withdrawal effects, including craving for cigarettes, negative affect, hypoarousal, and increased appetite. This study also assessed the depressive symptoms shown by smokers before and after they quit smoking. Control subjects showed a significant increase in depressive symptoms after smoking cessation, whereas the subjects given the nicotine skin patch were not as affected. If the subjects slipped and smoked a cigarette during the time they were wearing the patch, they were asked to rate the effects of that cigarette. These "slip" cigarettes were rated significantly lower in satisfaction and good taste by subjects in the nicotine patch group than by controls. The nicotine skin patch may improve smoking cessation rates both by reducing nicotine withdrawal effects and by reducing the reward of slips back to smoking. This latter effect may prove to be effective in preventing slips from turning into relapses.

Authors
Levin, ED; Westman, EC; Stein, RM; Carnahan, E; Sanchez, M; Herman, S; Behm, FM; Rose, JE
MLA Citation
Levin, ED, Westman, EC, Stein, RM, Carnahan, E, Sanchez, M, Herman, S, Behm, FM, and Rose, JE. "Nicotine skin patch treatment increases abstinence, decreases withdrawal symptoms, and attenuates rewarding effects of smoking." J Clin Psychopharmacol 14.1 (February 1994): 41-49.
PMID
8151002
Source
pubmed
Published In
Journal of Clinical Psychopharmacology
Volume
14
Issue
1
Publish Date
1994
Start Page
41
End Page
49

Inhalation of vapor from black pepper extract reduces smoking withdrawal symptoms.

Previous studies have suggested that sensory cues associated with cigarette smoking can suppress certain smoking withdrawal symptoms, including craving for cigarettes. In this study we investigated the subjective effects of a cigarette substitute delivering a vapor of black pepper essential oil. Forty-eight cigarette smokers participated in a 3-h session conducted after overnight deprivation from smoking. Subjects were randomly assigned to one of three conditions: one group of smokers puffed on a device that delivered a vapor from essential oil of black pepper; a second group puffed on the device with a mint/menthol cartridge, and a third group used a device containing an empty cartridge. Subjects puffed and inhaled ad libitum from the device throughout the session during which no smoking was allowed. Reported craving for cigarettes was significantly reduced in the pepper condition relative to each of the two control conditions. In addition, negative affect and somatic symptoms of anxiety were alleviated in the pepper condition relative to the unflavored placebo. The intensity of sensations in the chest was also significantly higher for the pepper condition. These results support the view that respiratory tract sensations are important in alleviating smoking withdrawal symptoms. Cigarette substitutes delivering pepper constituents may prove useful in smoking cessation treatment.

Authors
Rose, JE; Behm, FM
MLA Citation
Rose, JE, and Behm, FM. "Inhalation of vapor from black pepper extract reduces smoking withdrawal symptoms." Drug Alcohol Depend 34.3 (February 1994): 225-229.
PMID
8033760
Source
pubmed
Published In
Drug and Alcohol Dependence
Volume
34
Issue
3
Publish Date
1994
Start Page
225
End Page
229

Reducing Craving for Cigarettes While Decreasing Smoke Intake Using Capsaicin-Enhanced Low Tar Cigarettes

The effects on smoking behavior and subjective evaluation of adding capsaicin (a pungent principle of chili pepper) to a low tar and nicotine cigarette were studied in 12 cigarette smokers. In a 4-hr session, Ss inhaled smoke from 3 types of cigarettes: (a) low tar and nicotine cigarettes with capsaicin added; (b) low tar and nicotine cigarettes without capsaicin (control); and (c) commercial high tar and nicotine cigarettes. Ss puffed significantly less on the capsaicin cigarettes than on the other 2 types of cigarettes and reported greater reduction in cigarette craving after smoking capsaicin cigarettes than after smoking control low nicotine cigarettes. Estimated nicotine intake and respiratory tract sensations for the capsaicin cigarettes were also significantly higher than for the control cigarettes. These results support the view that respiratory tract sensations are important in reducing smokers' craving for cigarettes and modulating smoking behavior.

Authors
Behm, FM; Rose, JE
MLA Citation
Behm, FM, and Rose, JE. "Reducing Craving for Cigarettes While Decreasing Smoke Intake Using Capsaicin-Enhanced Low Tar Cigarettes." Experimental and Clinical Psychopharmacology 2.2 (1994): 143-153.
Source
scival
Published In
Experimental and Clinical Psychopharmacology
Volume
2
Issue
2
Publish Date
1994
Start Page
143
End Page
153

Combined Effects of Nicotine and Mecamylamine in Attenuating Smoking Satisfaction

Separate and combined effects of nicotine and the nicotinic antagonist mecamylamine were studied. Twelve smokers rated test cigarettes after administration of mecamylamine versus placebo capsules and nicotine versus nonnicotine preload. Smoking withdrawal symptoms, task performance, and cardiovascular activity were also measured. Mecamylamine attenuated smoking satisfaction, liking, and airway sensations. The nicotine preload similarly reduced the enjoyable aspects of subsequent test cigarettes, and this action of the preload was not prevented by mecamylamine. In contrast, mecamylamine blocked nicotine-related increases in heart rate and systolic blood pressure. Conversely, nicotine counteracted mecamylamine's effects on tapping speed and orthostatic blood pressure response. Although each drug offset potential side effects of the other, they acted in unison to attenuate smoking satisfaction and should be evaluated in combination for smoking cessation.

Authors
Rose, JE; Behm, FM; Westman, EC; Levin, ED; Stein, RM; Lane, JD; Ripka, GV
MLA Citation
Rose, JE, Behm, FM, Westman, EC, Levin, ED, Stein, RM, Lane, JD, and Ripka, GV. "Combined Effects of Nicotine and Mecamylamine in Attenuating Smoking Satisfaction." Experimental and Clinical Psychopharmacology 2.4 (1994): 328-344.
Source
scival
Published In
Experimental and Clinical Psychopharmacology
Volume
2
Issue
4
Publish Date
1994
Start Page
328
End Page
344

Intracerebroventricular nicotine and mecamylamine alter radial-arm maze performance in rats

In rats, the effects of an intracerebroventricular (ICV) nicotinic agonist nicotine (NIC), the nicotinic antagonist mecamylamine (MEC), and combinations of NIC + MEC were assessed in a radial-arm maze (RAM). In experiment 1, exploratory behavior was assessed in untrained rats (N = 13). The rats received 4 μg, 8.65 nmol NIC (NIC 4), 200 μg, 0.98 μmol MEC (MEC), and saline (SAL) ICV infusions. NIC 4 caused a significant increase in choice distribution compared to SAL (P < 0.025). In experiment 2, rats (N = 10) were trained to perform a working memory task for food reinforcement in the RAM. ICV doses of SAL, NIC 4, NIC 8, MEC, MECNIC 4, and MECNIC 8 were administered after completion of the training period. MEC caused a significant deficit in choice accuracy when compared to SAL (P < 0.025). This deficit was reversed when NIC 8 was coadministered with MEC (P < 0.05). There were no significant effects on choice latency for either study. The effects of ICV NIC and MEC on RAM performance are generally similar to their systemic effects in that NIC improves and MEC impairs choice accuracy. The reversal of the MEC-induced choice deficit by ICV NIC administration has not been reported with systemic administration. ICV MEC induces a choice accuracy deficit without increasing choice latency. This has not been seen with systemic MEC administration. The current result implies that the MEC-induced choice accuracy deficit did not result from MEC-induced sedation. The data indicate that previously reported changes in choice accuracy from peripherally administered NIC and MEC result from their central effects.

Authors
Brucato, FH; Levin, ED; Rose, JE; Swartzwelder, HS
MLA Citation
Brucato, FH, Levin, ED, Rose, JE, and Swartzwelder, HS. "Intracerebroventricular nicotine and mecamylamine alter radial-arm maze performance in rats." Drug Development Research 31.1 (1994): 18-23.
Source
scival
Published In
Drug Development Research
Volume
31
Issue
1
Publish Date
1994
Start Page
18
End Page
23

Saliva nicotine as an index of plasma levels in nicotine skin patch users.

This study examined whether salivary nicotine concentrations would provide a useful index of plasma concentrations in studies of the effects of transdermal nicotine administration. Twenty-four subject smokers abstained from smoking for 12 h prior to admission to a clinical research unit ward and for 36 h while remaining confined to the ward. Three doses of nicotine skin patches were applied to different groups of subjects, and blood and saliva samples were collected at several time points. Saliva flow was stimulated by three different methods: (a) sucking on a lemon candy, (b) dissolving a sugar cube in the mouth, and (c) chewing on parafilm. Nicotine and cotinine concentrations were measured in both saliva and blood using gas chromatography. There was a high correlation between blood and saliva values of nicotine (r = 0.82). Overall, saliva nicotine concentrations were approximately 8.1 times higher than those of plasma. Saliva and blood cotinine concentrations were also highly correlated (r = 0.94), replicating results of previous studies. Results suggest that saliva nicotine may be a useful marker of nicotine intake during nicotine skin patch treatment. Saliva collection may be advantageous under conditions in which blood collection is impractical and may provide greater sensitivity because of the high concentration of nicotine in saliva relative to that in blood.

Authors
Rose, JE; Levin, ED; Benowitz, N
MLA Citation
Rose, JE, Levin, ED, and Benowitz, N. "Saliva nicotine as an index of plasma levels in nicotine skin patch users." Ther Drug Monit 15.5 (October 1993): 431-435.
PMID
8249050
Source
pubmed
Published In
Therapeutic Drug Monitoring
Volume
15
Issue
5
Publish Date
1993
Start Page
431
End Page
435

Clinical trials using ascorbic acid aerosol to aid smoking cessation.

Sensory aspects of cigarette smoke are important for providing smoking satisfaction. In previous studies, we have found that substitution of the sensory cues of smoking with a citric acid aerosol significantly reduces craving for cigarettes and enhances smoking reduction and cessation with people trying to quit smoking cigarettes. In the current study, we conducted two clinical smoking cessation trials using an ascorbic acid aerosol as a sensory substitute. The cigarette substitute consisted of a cigarette-sized tube which delivered a fine aerosol of ascorbic acid (approx. 1 mg/puff, up to a maximum of 300 mg/day). Study 1 examined the overall effectiveness of the ascorbic acid smoking substitute device. One group of subjects which used the device and received clinical counseling was compared with another group which received only clinical counseling. The group using the device showed significantly greater abstinence rates at 3 weeks post-cessation. After the subjects stopped using the device, no difference in abstinence was detected. Study 2 was conducted to focus specifically on the role of tracheobronchial sensations in relieving craving for cigarettes. Two closely matched ascorbic acid delivery systems were compared. One device delivered fine particles of ascorbic acid that were targeted to reach the trachea, while the other delivered coarser particles of ascorbic acid that were not expected to reach the trachea or lower airways. An initial enhancement in smoking reduction was found for subjects using the fine particle device relative to those using the coarse particle device. However, by the end of treatment (5 weeks) both groups showed similar degrees of smoking reduction. For those who were abstinent from smoking at the end of treatment, craving for cigarettes and negative mood were both significantly lower for those using the fine particle device. Also, hunger for food was significantly lower in the fine particle device group. These results suggest that ascorbic acid delivered from a cigarette substitute may be effective in reducing smoking and promoting smoking abstinence.

Authors
Levin, ED; Behm, F; Carnahan, E; LeClair, R; Shipley, R; Rose, JE
MLA Citation
Levin, ED, Behm, F, Carnahan, E, LeClair, R, Shipley, R, and Rose, JE. "Clinical trials using ascorbic acid aerosol to aid smoking cessation." Drug Alcohol Depend 33.3 (October 1993): 211-223.
PMID
8261886
Source
pubmed
Published In
Drug and Alcohol Dependence
Volume
33
Issue
3
Publish Date
1993
Start Page
211
End Page
223

Chronic nicotine reverses working memory deficits caused by lesions of the fimbria or medial basalocortical projection.

Nicotine has been found in a variety of studies to improve performance in memory tasks. This study was conducted to determine if chronic nicotine administration is useful in counteracting the working memory deficits seen after lesions of the fimbria or the medial basalocortical projection. Rats were trained to asymptotic performance on a working memory version of the radial-arm maze. Then, they were given knife cut lesions of the fimbria or the medial basalocortical projection or underwent sham surgeries. At the time of surgery, rats in each treatment group were implanted with either nicotine-containing or placebo glass and Silastic pellets. Rats with fimbria or basalocortical lesions showed a significant decline in working memory performance. Chronic nicotine significantly improved choice accuracy in both lesioned and unlesioned rats. Nicotine treatment restored performance of the lesioned rats to control levels. These data show that in addition to improving memory performance in normal rats, nicotine can counteract lesion-induced memory impairments. Nicotine also may be useful for treatment of disease-related memory impairments such as seen in Alzheimer's disease.

Authors
Levin, ED; Christopher, NC; Briggs, SJ; Rose, JE
MLA Citation
Levin, ED, Christopher, NC, Briggs, SJ, and Rose, JE. "Chronic nicotine reverses working memory deficits caused by lesions of the fimbria or medial basalocortical projection." Brain Res Cogn Brain Res 1.3 (October 1993): 137-143.
PMID
8257869
Source
pubmed
Published In
Cognitive Brain Research
Volume
1
Issue
3
Publish Date
1993
Start Page
137
End Page
143

The nicotine patch in smoking cessation. A randomized trial with telephone counseling.

BACKGROUND: This study was conducted to determine the efficacy of the nicotine patch in smoking cessation when combined with self-help materials, three brief visits, and telephone counseling. METHODS: One hundred fifty-nine healthy volunteers who smoked at least one pack of cigarettes per day and desired to quit smoking were enrolled in a double-blind trial with 6-week treatment and 6-month follow-up periods. After review of self-help materials, subjects were randomly assigned to regimens of nicotine or placebo patches. Subjects wore two patches per day for 4 weeks (25 mg of nicotine per 24 hours), then one patch per day for 2 weeks. Return visits were at the ends of weeks 4 and 6. Telephone counseling was given during weeks 1, 2, 3, and 5. Abstinence at 6 weeks was defined as zero cigarettes smoked for the previous 28 days, verified by exhaled carbon monoxide less than 8 ppm at 4 weeks and 6 weeks. Abstinence at 3 and 6 months was defined as self-report of zero cigarettes since the previous contact, verified by carbon monoxide value at 6 months. RESULTS: Abstinence rates at 6 weeks, 3 months, and 6 months were 29.5%, 21.8%, and 20.5% in the active group, and 8.8%, 3.8%, and 2.5% in the placebo group (P < or = .001 for each comparison), respectively. Skin irritation was the main side effect, causing 1.3% to drop out. CONCLUSION: The nicotine patch is efficacious in smoking cessation over a 6-month period, when combined with only self-help materials, three brief visits, and telephone counseling.

Authors
Westman, EC; Levin, ED; Rose, JE
MLA Citation
Westman, EC, Levin, ED, and Rose, JE. "The nicotine patch in smoking cessation. A randomized trial with telephone counseling." Arch Intern Med 153.16 (August 23, 1993): 1917-1923.
PMID
8250653
Source
pubmed
Published In
Archives of internal medicine
Volume
153
Issue
16
Publish Date
1993
Start Page
1917
End Page
1923

Prenatal nicotine exposure and cognitive performance in rats.

In humans and animal models there is evidence that prenatal nicotine exposure causes lasting deficits in cognitive performance. The current study examined the cognitive effects of prenatal exposure of rats to 2 mg/kg/day of nicotine. This dose did not cause significant deficits in maternal weight gain, offspring litter size, or pup weight. The control offspring showed the normal ontogeny of spontaneous alternation from near chance (50%) performance to 80%-85% alternation. In contrast, the nicotine-exposed rats had the opposite progression with abnormally high alternation on days 22-30 and abnormally low alternation on days 35-52. Acquisition of choice accuracy performance on the radial-arm maze (RAM) was not altered in a major way by nicotine exposure. Minor nicotine-induced changes in choice accuracy were seen during the initial trials of acquisition. The nicotine exposed female offspring had a significantly longer response duration. Prenatal nicotine exposure did significantly alter the effects of subsequent drug challenges on choice accuracy performance. The nicotine-exposed male offspring were significantly more responsive to the amnestic effects of the nicotinic antagonist mecamylamine. In a subsequent challenge, the effects of the beta-adrenergic antagonist propranolol were examined. A significant dose-related impairment in choice accuracy was seen in the control rats. In contrast, the nicotine-exposed rats did not show any significant response to propranolol. This decreased responsiveness to adrenergic challenge parallels the reduction in adrenergic response to nicotine challenge we previously found in littermates to the rats of the current study. Prenatal nicotine exposure causes subtle alterations in cognitive performance that can be magnified by challenges of nicotinic and adrenergic systems.

Authors
Levin, ED; Briggs, SJ; Christopher, NC; Rose, JE
MLA Citation
Levin, ED, Briggs, SJ, Christopher, NC, and Rose, JE. "Prenatal nicotine exposure and cognitive performance in rats." Neurotoxicol Teratol 15.4 (July 1993): 251-260.
PMID
8413079
Source
pubmed
Published In
Neurotoxicology and Teratology
Volume
15
Issue
4
Publish Date
1993
Start Page
251
End Page
260

Chronic nicotinic stimulation and blockade effects on working memory.

Acute and chronic nicotine treatment has been found to improve learning and memory function in a variety of tasks. In several studies we have found that chronic nicotine infusion improves working memory performance. Replicating these results, the current study showed that chronic nicotine treatment (12mg/kg/day) significantly improved working memory performance in the radial-arm maze. The nicotine effect did not diminish during the 2 weeks following withdrawal. The nicotine-induced improvement was eliminated when the nicotinic antagonist mecamylamine (3mg/kg/day) was given concurrently, suggesting that the nicotine effect was mediated via actions on the nicotinic receptor. Surprisingly, when this chronic dose of mecamylamine was given alone, it caused a transient improvement in choice accuracy during the first week of administration. This improvement subsequently became attenuated and was not evident at all by the third and fourth weeks of administration.

Authors
Levin, ED; Briggs, SJ; Christopher, NC; Rose, JE
MLA Citation
Levin, ED, Briggs, SJ, Christopher, NC, and Rose, JE. "Chronic nicotinic stimulation and blockade effects on working memory." Behav Pharmacol 4.2 (April 1993): 179-182.
PMID
11224184
Source
pubmed
Published In
Behavioural Pharmacology
Volume
4
Issue
2
Publish Date
1993
Start Page
179
End Page
182

Role of nicotine dose and sensory cues in the regulation of smoke intake.

We investigated the role of nicotine dose and sensory cues in the regulation of ad lib smoke intake. The smoking behavior of 12 adult male smokers was assessed in three conditions, presenting either high-nicotine cigarette smoke (high nicotine, high sensory), diluted cigarette smoke (low nicotine, low sensory), or an aerosol containing cigarette smoke constituents suspended in solution, which was low in nicotine, yet high in sensory impact. Subjects showed marked compensatory increases in smoking with the dilute smoke conditions, whereas they puffed and inhaled the aerosol to a similar extent as the high-nicotine cigarette. Thus, subjects regulated their smoking behavior to equate sensory intensity rather than nicotine intake. Moreover, the aerosol and high-nicotine cigarette conditions lowered craving to a greater degree than the dilute smoke condition. Other mood indices, such as arousal and negative affect, were more effectively relieved by the high-nicotine dose condition. These results highlight the importance of sensory cues in the regulation of smoke intake and modulation of craving and suggest the clinical application of techniques for providing relief of cigarette craving during smoking cessation.

Authors
Rose, JE; Behm, FM; Levin, ED
MLA Citation
Rose, JE, Behm, FM, and Levin, ED. "Role of nicotine dose and sensory cues in the regulation of smoke intake." Pharmacol Biochem Behav 44.4 (April 1993): 891-900.
PMID
8469698
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
44
Issue
4
Publish Date
1993
Start Page
891
End Page
900

Clinical evaluation of a citric acid inhaler for smoking cessation.

In this study, we evaluated the efficacy of a hand-held inhaler as an adjunct to a smoking cessation behavioral program. The inhaler delivered a citric acid aerosol with tobacco smoke flavor. Seventy-four smokers were recruited for a 3-week smoking cessation trial. During the first 12 days of the cessation period, smokers used the citric acid aerosol inhaler instead of a cigarette whenever the urge to smoke occurred. The citric acid inhaler significantly reduced CO levels and enhanced rates of smoking abstinence for those with higher than average (34.2 ppm) baseline end-expired carbon monoxide (CO) levels. Craving for cigarettes and negative affect were also alleviated by the citric acid aerosol. These results suggest that the citric acid aerosol may promote successful smoking reduction or cessation in a subgroup of smokers and relieves withdrawal symptoms such as craving for cigarettes, a symptom difficult to treat with currently available nicotine replacement techniques.

Authors
Behm, FM; Schur, C; Levin, ED; Tashkin, DP; Rose, JE
MLA Citation
Behm, FM, Schur, C, Levin, ED, Tashkin, DP, and Rose, JE. "Clinical evaluation of a citric acid inhaler for smoking cessation." Drug Alcohol Depend 31.2 (January 1993): 131-138.
PMID
8436059
Source
pubmed
Published In
Drug and Alcohol Dependence
Volume
31
Issue
2
Publish Date
1993
Start Page
131
End Page
138

Sertraline attenuates hyperphagia in rats following nicotine withdrawal.

Chronic nicotine administration can decrease food consumption and body weight. Abrupt withdrawal from nicotine can cause the reverse effect, hyperphagia and rapid weight gain. In the current study, the efficacy of sertraline, a serotonin reuptake inhibitor, on nicotine withdrawal-induced hyperphagia and rapid weight gain was assessed in rats. Sertraline was found to be effective in reversing the increase in feeding that occurred after withdrawal from chronic nicotine administration. Sertraline caused a dose-related decrease in food consumption in control rats not given nicotine. Doses of 5 and 10 mg/kg/day caused significant decreases while 2.5 mg/kg/day caused a slight though nonsignificant decrease in food consumption. Rats in which nicotine was abruptly withdrawn after 3 weeks of administration showed a significant increase in food consumption relative to controls. This increase was eliminated by the high dose of sertraline (10 mg/kg/day), but not by the lower two doses (2.5 and 5 mg/kg/day). Water consumption was affected in a similar fashion. Body weight gain was also affected by sertraline. During the first week after nicotine withdrawal, rats rapidly gained weight, but sertraline attenuated this. The 10-mg/kg dose of sertraline significantly attenuated the nicotine withdrawal-induced weight gain. These results suggest that sertraline can counteract the hyperphagia and rapid weight gain associated with nicotine withdrawal, and might therefore be a useful adjunct to smoking cessation.

Authors
Levin, ED; Briggs, SJ; Christopher, NC; Rose, JE
MLA Citation
Levin, ED, Briggs, SJ, Christopher, NC, and Rose, JE. "Sertraline attenuates hyperphagia in rats following nicotine withdrawal." Pharmacol Biochem Behav 44.1 (January 1993): 51-61.
PMID
8430129
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
44
Issue
1
Publish Date
1993
Start Page
51
End Page
61

Pharmacokinetics of a transdermal nicotine patch compared to nicotine gum

A new transdermal nicotine delivery system (TBS-NCT) was investigated in laboratory and clinical studies with healthy cigarette smokers. Plasma nicotine concentration time profiles were characterized during and after 24-hr application of three doses of TBS-NCT and during and after a 6-hr regimen of nicotine polacrilex gum. Pharmacokinetic anlaysis revealed dose-related plasma concentrations for transdermal treatments, bracketing the concentrations obtained from nicotine gum. The TBS-NCT system was also well tolerated during a subsequent 4-week open trial and demonstrated a 40% success rate for smoking cessation during the course of the trial. Overall, the TBS-CNT system appears suitable for once-daily application as an aid in smoking cessation treatments.

Authors
Lane, JD; Westman, EC; Ripka, GV; Wu, J; Chiang, C-C; Rose, JE
MLA Citation
Lane, JD, Westman, EC, Ripka, GV, Wu, J, Chiang, C-C, and Rose, JE. "Pharmacokinetics of a transdermal nicotine patch compared to nicotine gum." Drug Development and Industrial Pharmacy 19.16 (1993): 1999-2010.
Source
scival
Published In
Drug Development and Industrial Pharmacy
Volume
19
Issue
16
Publish Date
1993
Start Page
1999
End Page
2010

Persistence of chronic nicotine-induced cognitive facilitation.

Nicotine has been found in a variety of species and behavioral paradigms to improve memory performance. The beneficial effect of nicotine has been seen after both acute and chronic administration. Interestingly, improved performance has been seen 24 h after acute injection and for at least 2 weeks after chronic administration. However, it is not clear from previous studies whether the persistence of the improved performance represents a true carryover of the drug effect or is due to the behavioral experience while under nicotine's effect. The current study was conducted to determine whether the facilitating effect of nicotine on learning and memory performance could be seen after withdrawal even if there was no behavioral training during the period of chronic nicotine administration. Rats were administered nicotine chronically for 3 weeks but were not tested during that time. Starting 1 week after withdrawal they were trained on a working memory paradigm in an eight-arm radial maze. The nicotine-treated rats started out at control-like levels of performance, but showed significantly faster learning as detected by three different measures of choice accuracy. By the final phase of testing the control subjects had caught up with the nicotine-treated rats. After the acquisition phase, acute challenges with the nicotinic and muscarinic antagonists, mecamylamine and scopolamine, did not elicit any differential effects in the nicotine-treated and control groups. The current study demonstrated that nicotine-induced cognitive facilitation persists for at least 4 weeks after withdrawal and does not depend upon behavioral test experience under the influence of the drug. The mechanism for this persisting effect is not currently understood.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Levin, ED; Briggs, SJ; Christopher, NC; Rose, JE
MLA Citation
Levin, ED, Briggs, SJ, Christopher, NC, and Rose, JE. "Persistence of chronic nicotine-induced cognitive facilitation." Behav Neural Biol 58.2 (September 1992): 152-158.
PMID
1456935
Source
pubmed
Published In
Behavioral and Neural Biology
Volume
58
Issue
2
Publish Date
1992
Start Page
152
End Page
158

Nicotine psychopharmacology

Authors
Stolerman, I; Rose, J
MLA Citation
Stolerman, I, and Rose, J. "Nicotine psychopharmacology." Journal of Psychopharmacology 6.4 (July 1992): 545-546.
Source
crossref
Published In
Journal of Psychopharmacology
Volume
6
Issue
4
Publish Date
1992
Start Page
545
End Page
546
DOI
10.1177/026988119200600416

Concurrent agonist-antagonist administration for the analysis and treatment of drug dependence.

Two key strategies for the treatment of drug dependence involve the use of agonists to substitute for the abused drug and the use of antagonists to block the reinforcing actions maintaining drug self-administration. A different strategy for the treatment of drug dependence is outlined, comprising the concurrent administration of an agonist and an antagonist. Concurrent administration of an agonist with an antagonist, in the proper ratio, should produce maximal occupancy of receptors and attenuation of the reinforcing actions of the abused drug. The addict would be relatively "insulated" from the reinforcing effects of the abused drug; at the same time the balance of agonist and antagonist effects is predicted to prevent withdrawal symptoms or intoxication resulting from an under- or over-stimulation of drug receptors. Advantages over the use of agonists alone and antagonists alone, and over mixed agonist-antagonist molecules, are discussed. Application of concurrent agonist-antagonist administration to the analysis of mechanisms underlying nondrug reinforcement and to the treatment of disorders involving receptor disregulation is also described.

Authors
Rose, JE; Levin, ED
MLA Citation
Rose, JE, and Levin, ED. "Concurrent agonist-antagonist administration for the analysis and treatment of drug dependence." Pharmacol Biochem Behav 41.1 (January 1992): 219-226. (Review)
PMID
1539072
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
41
Issue
1
Publish Date
1992
Start Page
219
End Page
226

Nicotinic and muscarinic interactions and choice accuracy in the radial-arm maze.

Muscarinic acetylcholine (ACh) systems have long been known to be necessary for accurate performance in cognitive tests. Nicotinic ACh systems have been shown to be involved as well. However, there is only a limited amount of information concerning the interactions of these two branches of the ACh transmitter system. The current study was conducted to investigate the improvement in choice accuracy caused by muscarinic and nicotinic agonists and how it is affected by antagonists of these systems. Adult female Sprague-Dawley strain rats (N = 11) were trained on a working memory task in an 8-arm radial maze. Acute injections of the muscarinic and nicotinic agonists, pilocarpine (PILO, 1.0 mg/kg) and nicotine (NIC, 0.2 mg/kg), were made alone or in combination with the muscarinic and nicotinic antagonists, scopolamine (SCOP, 0.1 mg/kg) and mecamylamine (MEC, 10 mg/kg). NIC administration caused a significant improvement in choice accuracy compared with saline (p less than 0.01) and PILO caused a marginally significant improvement in choice accuracy (p less than 0.06). The combination of these nicotinic and muscarinic agonists did not cause an additive improvement. However, the improvement caused by either agonist was reversed by both nicotinic or muscarinic antagonists. This reversal was more complete for NIC than PILO despite the fact that NIC caused a greater improvement than PILO. These results suggest that muscarinic and nicotinic components of the ACh system, which are both important for cognitive function, interact in important ways. These interactions may be critical to consider when devising treatments for cognitive dysfunction associated with cholinergic hypofunction such as with Alzheimer's disease.

Authors
Levin, ED; Rose, JE
MLA Citation
Levin, ED, and Rose, JE. "Nicotinic and muscarinic interactions and choice accuracy in the radial-arm maze." Brain Res Bull 27.1 (July 1991): 125-128.
PMID
1933424
Source
pubmed
Published In
Brain Research Bulletin
Volume
27
Issue
1
Publish Date
1991
Start Page
125
End Page
128

The effects of smoking-related sensory cues on psychological stress.

Previous studies have shown that the sensory cues of cigarette smoking are important for smoking satisfaction and craving reduction. Sensory cues in the absence of pharmacological doses of nicotine have been found to be moderately satisfying and to reduce craving. The current study was conducted to determine if administration of the sensory cues of cigarette smoking with minimal nicotine would also provide relief from mild anxiety associated with anticipation of a difficult anagram test. This test has previously been shown to be sensitive to the anxiety relieving effects of cigarette smoking. Compared to the placebo control condition, the sensory condition caused a significant alleviation of the stress as measured by components of the Spielberger scale for anxiety. The addition of cigarette smoke containing 0.5 mg of nicotine to the sensory cues caused a slight though nonsignificant enhancement of the stress alleviation. These results demonstrate that sensory cues of smoking can provide similar effects as nicotine containing cigarettes with regard to stress alleviation. Previous studies had shown that sensory cues are important for the consumptive aspects of smoking (i.e., smoking satisfaction and craving reduction). The current study shows that sensory cues are important for other effects of smoking as well.

Authors
Levin, ED; Rose, JE; Behm, F; Caskey, NH
MLA Citation
Levin, ED, Rose, JE, Behm, F, and Caskey, NH. "The effects of smoking-related sensory cues on psychological stress." Pharmacol Biochem Behav 39.2 (June 1991): 265-268.
PMID
1946567
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
39
Issue
2
Publish Date
1991
Start Page
265
End Page
268

Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking.

Research on smoking cessation has increasingly focussed on pharmacological aspects of nicotine and nicotine withdrawal. However, cigarette smoking also provides a characteristic set of sensory cues. These sensory aspects of smoking are important to address in that they may be potent conditioned reinforcing stimuli linked to the actions of nicotine. The repetition of the smoking act thousands of times per year by a moderately heavy smoker leads to a strong conditioned association between the sensory aspects of smoking (the putative CS) and the pharmacological effects of nicotine (the putative UCS). Strategies for disrupting CS-UCS associations may be useful in developing more effective smoking cessation treatments. These include: counterconditioning of the CS; presenting the CS alone; presenting the CS with the UCS but pharmacologically blocking the UCS; and presenting the CS and UCS in an unconnected fashion. The role of sensory cues in alleviating craving for cigarettes is discussed, and specific techniques for duplicating relevant sensory aspects of smoking without delivering significant doses of nicotine are described. The combination of nicotine and nicotinic antagonists to block primary reinforcement and hasten extinction of conditioned reinforcement is also considered.

Authors
Rose, JE; Levin, ED
MLA Citation
Rose, JE, and Levin, ED. "Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking." Br J Addict 86.5 (May 1991): 605-609. (Review)
PMID
1859927
Source
pubmed
Published In
British Journal of Addiction
Volume
86
Issue
5
Publish Date
1991
Start Page
605
End Page
609

Interactive effects of D1 and D2 agonists with scopolamine on radial-arm maze performance.

Pharmacological blockade of muscarinic cholinergic (ACh) receptors has been found to impair choice accuracy in a variety of tasks including the radial-arm maze. The cognitive impairment caused by the muscarinic antagonist scopolamine is reversed by the dopaminergic (DA) antagonist haloperidol as well as the selective D1 antagonist SCH 23390. In the current study, interactions were studied between scopolamine and selective agonists of D1 (SCH 38393) and D2 (quinpirole) receptors. Surprisingly, the D1 agonist SKF 38393 was found to significantly alleviate the scopolamine-induced choice accuracy deficit. In contrast, the D2 agonist quinpirole was not found to significantly alter the effects of scopolamine on choice accuracy but did have supra-additive effects of increasing choice latency. Both the D1 agonist SKF 38393 and the D1 antagonist SCH 23390 have been found to reverse the choice accuracy deficit caused by scopolamine and the deficit resulting from lesions of the medial projection from the basal forebrain to the cortex. Possible mechanisms for these effects are discussed.

Authors
Levin, ED; Rose, JE
MLA Citation
Levin, ED, and Rose, JE. "Interactive effects of D1 and D2 agonists with scopolamine on radial-arm maze performance." Pharmacol Biochem Behav 38.2 (February 1991): 243-246.
PMID
1676165
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
38
Issue
2
Publish Date
1991
Start Page
243
End Page
246

Psychophysiological interactions between caffeine and nicotine.

The interactive effects of caffeine and nicotine were studied in twelve subjects. Mood and physiologic responses to the pharmacologic components nicotine and caffeine were measured, while controlling for the sensory/behavioral aspects of smoking and coffee drinking. Two experimental sessions presented a caffeine x nicotine design, with caffeinated or decaffeinated coffee followed at thirty-minute intervals by controlled inhalations of nicotine and nonnicotine smoke. Results showed that there was a significant interactive effect of caffeine and nicotine on subjective arousal such that nicotine decreased arousal only in the presence of caffeine. These findings extend previous work showing interactive effects of caffeine and self-titrated doses of cigarette smoke in affecting subjective arousal. The effects of nicotine on subjective arousal may, therefore, depend not only on nicotine dose, but also on the presence of caffeine. Heart rate was increased by nicotine and both systolic and diastolic blood pressures were elevated by caffeine. Caffeine also potentiated the increase in diastolic blood pressure resulting from smoke inhalations, but this occurred irrespective of nicotine dose.

Authors
Rose, JE; Behm, FM
MLA Citation
Rose, JE, and Behm, FM. "Psychophysiological interactions between caffeine and nicotine." Pharmacol Biochem Behav 38.2 (February 1991): 333-337.
PMID
2057503
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
38
Issue
2
Publish Date
1991
Start Page
333
End Page
337

Tar, CO and Δ9-THC delivery from the 1st and 2nd halves of a marijuana cigarette

Previous in vitro studies suggest that, with successive puffs from a marijuana cigarette, delta-9-THC becomes concentrated in the remaining uncombusted portion of the cigarette. These observations are consistent with the common practice of smoking marijuana cigarettes to a smaller butt length than that to which tobacco cigarette. are smoked. The purpose of the present study was to compare the delivery of delta-9-THC, as well as total insoluble smoke particulates (tar) and carbon monoxide, from the distal ("first") versus the proximal ("second") halves of a standard marijuana cigarette during "natural" smoking of marijuana. On 4 separate days, ten habitual marijuana users smoked nearly all or approximately 1 2 of a standard marijuana cigarette (83 mm length; 800-900 mg; 1.24% THC), as follows: day 1, "whole" cigarette (60 mm smoked, leaving a 23-mm butt); day 2, "first" half (first 30 mm); day 3, "second" half (second 30 mm) after the "first" half was presmoked with a syringe; and day 4, "second" half after the "first" half was excised. A previously described smoking apparatus (20) was used for measurement of puff volume and inhaled tar. Puff volume and number were allowed to vary spontaneously (provided that the specified length of cigarette was consumed), while inhaled volume (1.5 liters), breathholding time (14 s) and interpuff interval (30 s) were held constant. Blood samples were withdrawn prior to smoking and serially after completion of smoking for analysis of blood carboxy-hemoglobin (COHb) and serum delta-9-THC. Heart rate was measured before and 5 min after smoking. Subjects rated their level of "high" 20 min after completion of smoking. Compared to the distal half, smoking the proximal half of a marijuana cigarette delivered more tar, carbon monoxide and THC to the smoker's lungs, as indicated by a greater amount of inhaled tar and a larger boost in both blood carboxyhemoglobin and serum THC. In addition, boosts in blood COHb and serum THC were significantly greater following smoking the proximal half after the distal half had been presmoked rather than excised. These findings are probably due to 1) less rod filtration of insoluble particulates, 2) increased concentration in the proximal half of the cigarette of carbonaceous material and THC volatilized by prior combustion of the distal half, and 3) possible differences in burn rate due to effects of precombustion of the distal half on moisture content of the proximal half. Clinical implications of these findings are that smoking fewer marijuana cigarettes down to a shorter butt length to deliver more THC and achieve a greater "high" is potentially more harmful to cardiorespiratory health than consuming a comparable amount of marijuana contained in more cigarettes smoked to a longer butt length. © 1991.

Authors
Tashkin, DP; Gliederer, F; Rose, J; Chang, P; Hui, KK; Yu, JL; Wu, T-C
MLA Citation
Tashkin, DP, Gliederer, F, Rose, J, Chang, P, Hui, KK, Yu, JL, and Wu, T-C. "Tar, CO and Δ9-THC delivery from the 1st and 2nd halves of a marijuana cigarette." Pharmacology, Biochemistry and Behavior 40.3 (1991): 657-661.
PMID
1666924
Source
scival
Published In
Pharmacology Biochemistry and Behavior
Volume
40
Issue
3
Publish Date
1991
Start Page
657
End Page
661

Effects of varying marijuana smoking profile on deposition of tar and absorption of CO and delta-9-THC

We investigated the effects of previously observed differences in smoking technique for marijuana (M) versus tobacco (T) on the amount of inhaled tar, the percentage retention of inhaled tar in the lung, the pre- to postcigarette boost in blood carboxy-hemoglobin (COHb) and in serum delta-9-tetrahydrocannabinol (THC concentrations), and psychophysiologic responses to THC (increased heart rate and subjective "high"). Ten healthy, habitual smokers of M were studied on 6 separate days. On each day, subjects smoked a single M cigarette (∼900 mg, 1.24% delta-9-THC) using one of 6 different smoking profiles typical for marijuana [puff volume (PV) ∼70 ml; breathholding time, (BHT) 14-16s] or tobacco (PV ∼ ml; BHT 4-5 s) or a combination of the two techniques (PV ∼70 ml and BHT 4-5 s; or PV ∼45 ml and BHT 14-16s). Inhaled volume (1.5 liters), interpuff interval (30 s) and number of puffs (6) were all fixed, except that for the ∼45-ml PV condition, the number of puffs was increased to 10 in 2 additional sessions to standardize the total amount of cigarette consumed to that of the ∼70 ml PV condition. The longer BHT significantly increased both percent retention of tar in the lung and the pre- to postsmoking rise in blood COHb, serum THC and heart rate, independent of puff volume and number. In contrast, the larger PV had no significant influence on these variables for the same amount of cigarette consumed. The longer BHT (and not the larger PV) characteristics of M smoking contributes to the greater COHb boost and lung retention of inhaled tar during M compared to T smoking. In addition, the longer BHT appears to enhance THC absorption. © 1991.

Authors
Tashkin, DP; Gliederer, F; Rose, J; Chang, P; Hui, KK; Yu, JL; Wu, T-C
MLA Citation
Tashkin, DP, Gliederer, F, Rose, J, Chang, P, Hui, KK, Yu, JL, and Wu, T-C. "Effects of varying marijuana smoking profile on deposition of tar and absorption of CO and delta-9-THC." Pharmacology, Biochemistry and Behavior 40.3 (1991): 651-656.
PMID
1666923
Source
scival
Published In
Pharmacology Biochemistry and Behavior
Volume
40
Issue
3
Publish Date
1991
Start Page
651
End Page
656

Cholinergic-dopaminergic interactions in cognitive performance.

Both acetylcholinergic (ACh) and dopaminergic (DA) systems have been found to be crucial for the maintenance of accurate cognitive performance. In a series of studies examining those aspects of cognitive function revealed by the radial-arm maze, we have found that these two neurotransmitter systems interact in a complex fashion. Choice accuracy deficits in the radial-arm maze can be induced by blockade of either muscarinic- or nicotinic-ACh receptors. The choice accuracy deficit induced by blockade of muscarinic receptors with scopolamine can be reversed by the DA receptor blocker, haloperidol. The specific DA D1 blocker SCH 23390 also has this effect, whereas the specific D2 blocker raclopride does not, implying that it is D1 blockade that is critical for reversing the scopolamine effect. On the other hand, the choice accuracy deficit induced by nicotinic blockade with mecamylamine is potentiated by haloperidol. This effect is also seen with the D2 antagonist raclopride, but not with the D1 antagonist SCH 23390, implying that it is the D2 receptor which is important for the potentiation of the mecamylamine effect. The relevance of the D2 receptor for nicotinic actions on cognitive function is emphasized by the finding that the selective D2 agonist LY 171555 reverses the choice accuracy deficit caused by mecamylamine. Nicotinic and muscarinic blockade are synergistic in the deficit they produce. Antagonist doses subthreshold when given alone produce a pronounced impairment when given together. This latter deficit can be reversed by the D2 agonist LY 171555. These studies have outlined the complex nature of ACh-DA interactions with regard to cognitive function. Possible neural circuits for these interactions are discussed. The effectiveness of these selective DA treatments in reversing cognitive deficits due to ACh underactivation suggests a novel approach to treating cognitive dysfunction in syndromes such as Alzheimer's disease.

Authors
Levin, ED; McGurk, SR; Rose, JE; Butcher, LL
MLA Citation
Levin, ED, McGurk, SR, Rose, JE, and Butcher, LL. "Cholinergic-dopaminergic interactions in cognitive performance." Behav Neural Biol 54.3 (November 1990): 271-299. (Review)
PMID
2078161
Source
pubmed
Published In
Behavioral and Neural Biology
Volume
54
Issue
3
Publish Date
1990
Start Page
271
End Page
299

The use of flavor in cigarette substitutes.

Cigarette smokers identify flavor as an important factor in the pleasure derived from smoking and for their choice of cigarette brand. The issue of cigarette flavor has received a great deal of study by cigarette manufacturers but relatively little by academic investigators. The paucity of literature is particularly acute in terms of the importance of flavor in cigarette substitutes, which are used to help people to reduce or quit smoking. In the current study, five different types of flavors added to a plastic cigarette substitute were assessed in experienced smokers. There were two menthol-like flavors and three tobacco-like flavors. Two groups of smokers were tested: menthol smokers and "regular" (non-menthol) smokers. Both types of smokers liked the two menthol flavors significantly more than placebo and rated the menthol flavors and the cigarette flavor as significantly more satisfying than placebo. Craving was differentially reduced in the two groups of smokers. Menthol smokers showed a small reduction in craving with the placebo, with a significant enhancement of this reduction seen with the addition of the "EZ Quit" menthol flavor.

Authors
Levin, ED; Behm, F; Rose, JE
MLA Citation
Levin, ED, Behm, F, and Rose, JE. "The use of flavor in cigarette substitutes." Drug Alcohol Depend 26.2 (October 1990): 155-160.
PMID
2242716
Source
pubmed
Published In
Drug and Alcohol Dependence
Volume
26
Issue
2
Publish Date
1990
Start Page
155
End Page
160

Development of a citric acid aerosol as a smoking cessation aid.

The satisfaction derived from smoking depends not only on the pharmacological effects of nicotine but also the sensory stimulation from smoke inhalation, particularly the tracheal 'scratch'. In a previous study, we found that a citric acid aerosol produces a tracheal 'scratch' and provides some of the same satisfaction as cigarette smoke. In the present study, we evaluated a new pocket-sized device for delivering a citric acid aerosol and examined some of the important variables for providing a satisfying substitute for cigarettes. In the first experiment, volunteers who smoked at least 10 cigarettes per day compared a citric acid aerosol (either alone or with flavor additives) to a cigarette and a placebo. The addition of cigarette smoke flavor was found to best enhance the satisfaction provided by the citric acid aerosol. In the second experiment, smokers were given compact citric acid inhalers to use throughout 8 h of cigarette deprivation. The degree of satisfaction was highly correlated with the intensity of throat sensation provided by the aerosol. This citric acid aerosol inhaler may provide a useful tool for smokers while trying to quit smoking.

Authors
Levin, ED; Rose, JE; Behm, F
MLA Citation
Levin, ED, Rose, JE, and Behm, F. "Development of a citric acid aerosol as a smoking cessation aid." Drug Alcohol Depend 25.3 (June 1990): 273-279.
PMID
2189719
Source
pubmed
Published In
Drug and Alcohol Dependence
Volume
25
Issue
3
Publish Date
1990
Start Page
273
End Page
279

Transdermal nicotine facilitates smoking cessation.

The efficacy of a transdermal nicotine patch in facilitation of smoking cessation was evaluated in a randomized double-blind trial. Sixty-five smokers who were highly dependent on cigarettes participated in the study, which included a behavioral smoking-cessation program. The rates of continuous abstinence were significantly higher in the nicotine group both initially (55% versus 34%) and at 3 weeks (18% versus 6%). Certain smoking withdrawal symptoms, including negative affect and hypoarousal, were effectively relieved by the nicotine patch. There was a trend toward a reduction in cigarette craving, whereas hunger and habit withdrawal symptoms were not affected. The main side effect associated with the nicotine patch was skin irritation. These findings suggest that a nicotine skin patch may be a useful aid to smoking cessation; however, the combination of other techniques with nicotine replacement may provide a more effective treatment for symptoms such as craving for cigarettes.

Authors
Rose, JE; Levin, ED; Behm, FM; Adivi, C; Schur, C
MLA Citation
Rose, JE, Levin, ED, Behm, FM, Adivi, C, and Schur, C. "Transdermal nicotine facilitates smoking cessation." Clin Pharmacol Ther 47.3 (March 1990): 323-330.
PMID
2178852
Source
pubmed
Published In
Clinical Pharmacology & Therapeutics (Nature)
Volume
47
Issue
3
Publish Date
1990
Start Page
323
End Page
330

Chronic nicotine and withdrawal effects on radial-arm maze performance in rats.

Rats were tested for choice accuracy in an eight-arm radial maze during and after chronic administration of nicotine via subcutaneously implanted glass and Silastic capsules. Nicotine administration significantly improved choice accuracy relative to controls. The effect gradually became apparent over the first 2 weeks of exposure and persisted through the third week. Surprisingly, the significant facilitation of the nicotine-treated rats relative to controls continued for 2 weeks after the end of nicotine administration. No effects of nicotine were seen on choice latency or the strategy to make adjacent arm entries.

Authors
Levin, ED; Lee, C; Rose, JE; Reyes, A; Ellison, G; Jarvik, M; Gritz, E
MLA Citation
Levin, ED, Lee, C, Rose, JE, Reyes, A, Ellison, G, Jarvik, M, and Gritz, E. "Chronic nicotine and withdrawal effects on radial-arm maze performance in rats." Behav Neural Biol 53.2 (March 1990): 269-276.
PMID
2331235
Source
pubmed
Published In
Behavioral and Neural Biology
Volume
53
Issue
2
Publish Date
1990
Start Page
269
End Page
276

Characterization of the cognitive effects of combined muscarinic and nicotinic blockade.

Choice accuracy performance in the radial-arm maze is dependent upon the integrity of both the nicotinic and muscarinic cholinergic receptors. Pharmacological blockade of either of these subtypes of cholinergic receptors with mecamylamine or scopolamine impairs choice accuracy in the radial-arm maze. We have previously demonstrated that the performance deficit caused by muscarinic blockade is exacerbated in at least an additive fashion by coadministration of the nicotinic antagonist, mecamylamine. In the present study, it was found that mecamylamine and scopolamine act together in a greater than additive fashion in disrupting radial-arm maze choice accuracy. When doses of these drugs which do not by themselves cause significant impairments in choice accuracy are given together, they induce a pronounced impairment. Previous results have shown that the adverse effects of nicotinic blockade could be reversed by the dopaminergic D2 agonist LY 171555. In this study, this drug was found to attenuate the cognitive impairment caused by combined nicotinic and muscarinic blockade. On the other hand, the dopaminergic D1 antagonist SCH 23390 which has previously been shown to reverse the adverse effects of muscarinic blockade was not found in this study to attenuate the impairment of combined nicotinic and muscarinic blockade. Since combined nicotinic and muscarinic blockade approximates generalized cholinergic underactivation, treatments like LY 171555, which attenuate the adverse effects of this combined blockade, may be useful in treating syndromes like Alzheimer's disease, which are characterized by generalized cholinergic loss.

Authors
Levin, ED; Rose, JE; McGurk, SR; Butcher, LL
MLA Citation
Levin, ED, Rose, JE, McGurk, SR, and Butcher, LL. "Characterization of the cognitive effects of combined muscarinic and nicotinic blockade." Behav Neural Biol 53.1 (January 1990): 103-112.
PMID
1967931
Source
pubmed
Published In
Behavioral and Neural Biology
Volume
53
Issue
1
Publish Date
1990
Start Page
103
End Page
112

Low-nicotine regenerated smoke aerosol reduces desire for cigarettes.

We have developed a method of producing an aerosol with many of the sensory qualities of cigarette smoke, but with only 3% of the tar and nicotine and none of the carbon monoxide of a typical commercial cigarette. The aerosol was generated from a suspension of 1% cigarette smoke condensate in 10% ethanol. The aerosol, generated with an ultrasonic nebulizer, resembled smoke visually but had a larger particle size than cigarette smoke (3.5 microns vs. 0.5 micron mass median diameter). Twelve smokers rated blocks of 10 puffs of aerosolized smoke solution, a popular commercial cigarette, and an unlit cigarette (control). The blocks of puffs were evaluated for sensory qualities and smoking satisfaction obtained. The rated strength of the smoke aerosol was comparable to that of the commercial cigarette. The aerosol was rated significantly more desirable and more satisfying than the control, though not as desirable as the commercial cigarette. Surprisingly, the smoke aerosol reduced self-reported desire for cigarettes as much as the commercial cigarette. This new method is a promising approach for evaluating the role of sensory cues in smoking, and it may also be useful as a clinical tool for smoking cessation.

Authors
Behm, FM; Levin, ED; Lee, YK; Rose, JE
MLA Citation
Behm, FM, Levin, ED, Lee, YK, and Rose, JE. "Low-nicotine regenerated smoke aerosol reduces desire for cigarettes." J Subst Abuse 2.2 (1990): 237-247.
PMID
2136112
Source
pubmed
Published In
Journal of Substance Abuse
Volume
2
Issue
2
Publish Date
1990
Start Page
237
End Page
247

Reversal of a mecamylamine-induced cognitive deficit with the D2 agonist, LY 171555.

Pharmacological blockade of either nicotinic or muscarinic cholinergic receptors has been found to impair choice accuracy in the radial-arm maze. Simultaneous blockade of both of these receptor types causes an additive impairment. However, despite these common effects, nicotinic and muscarinic receptors have been found to have differential involvement with dopamine receptors. The cognitive impairment caused by the muscarinic antagonist scopolamine is reversed by the D1 antagonist SCH 23390 but is unaffected by the D2 antagonist raclopride. In contrast, the cognitive impairment caused by the nicotinic antagonist mecamylamine is unaffected by SCH 23390 but is potentiated by raclopride. In the current study, the D2 agonist LY 171555 was found to be effective in reversing the radial-arm maze choice accuracy impairment caused by mecamylamine. In contrast, the D1 agonist SKF 38393 was not found to be effective. Thus, we have found selective dopaminergic D1 and D2 treatments which counteract the adverse cognitive effects of either nicotinic or muscarinic blockade. A combination of these treatments may be useful in treating the cognitive effects of generalized cholinergic underactivation.

Authors
Levin, ED; McGurk, SR; Rose, JE; Butcher, LL
MLA Citation
Levin, ED, McGurk, SR, Rose, JE, and Butcher, LL. "Reversal of a mecamylamine-induced cognitive deficit with the D2 agonist, LY 171555." Pharmacol Biochem Behav 33.4 (August 1989): 919-922.
PMID
2575760
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
33
Issue
4
Publish Date
1989
Start Page
919
End Page
922

Mecamylamine increases nicotine preference and attenuates nicotine discrimination.

Eight subjects evaluated various qualities of cigarette smoke after being given a range of doses (0, 2.5, 10 and 20 mg) of the nicotinic receptor blocker mecamylamine. In one test condition, subjects were given either high or low nicotine tobacco smoke to determine the effects of mecamylamine on their subjective responses. In another test condition, subjects were allowed to adjust the nicotine dose level of the smoke to determine the effects of mecamylamine on dose preference. When the subjects evaluated puffs of smoke with high and low nicotine content, mecamylamine caused a dose-related decrease in the self-rated strength and harshness of the high nicotine dose level smoke. In contrast, there was little effect on the low dose smoke. At the highest mecamylamine dose (20 mg) there was no significant difference in the ratings of high and low nicotine cigarettes. Low doses of mecamylamine decreased the reported desire for a cigarette, and also attenuated the reduction in desire for a cigarette caused by smoking. When the subjects were allowed to select their preferred level of nicotine intake using a smoke mixing device, the 10 and 20 mg doses of mecamylamine caused a significant increase in self-administered nicotine dose level. Despite this compensatory increase in nicotine self-administration, the reduction in desire for a cigarette after smoking was still less than after placebo.

Authors
Rose, JE; Sampson, A; Levin, ED; Henningfield, JE
MLA Citation
Rose, JE, Sampson, A, Levin, ED, and Henningfield, JE. "Mecamylamine increases nicotine preference and attenuates nicotine discrimination." Pharmacol Biochem Behav 32.4 (April 1989): 933-938.
PMID
2798542
Source
pubmed
Published In
Pharmacology Biochemistry and Behavior
Volume
32
Issue
4
Publish Date
1989
Start Page
933
End Page
938

Anxiolytic effects of smoking associated with four stressors.

There is a widespread belief that cigarette smoking alleviates stress. The literature reveals conflicting results on the anxiolytic effects of smoking. This study was designed to replicate a report that smoking (a) reduced subjective anxiety induced by stressful anagrams and (b) increased pain threshold for a cold pain task. This study (N = 15) included two other stressors: white noise and an auditory vigilance task. A significant Time x Condition (smoking vs. deprived) interaction was found for Spielberger State Anxiety Inventory scores in the anagram task. A borderline significant interaction effect was found for the cold pain task. No significant effects were found with the two other tasks. These results provide partial support for the popular notion that smoking mitigates stress-induced anxiety. No difference was found between the smoking and deprived conditions for either pain threshold or pain endurance.

Authors
Jarvik, ME; Caskey, NH; Rose, JE; Herskovic, JE; Sadeghpour, M
MLA Citation
Jarvik, ME, Caskey, NH, Rose, JE, Herskovic, JE, and Sadeghpour, M. "Anxiolytic effects of smoking associated with four stressors." Addictive behaviors 14.4 (January 1989): 379-386.
PMID
2782121
Source
epmc
Published In
Addictive Behaviors
Volume
14
Issue
4
Publish Date
1989
Start Page
379
End Page
386
DOI
10.1016/0306-4603(89)90025-7

Controlling puff volume without disrupting smoking topography

In studies of the behavioral and physiological effects of cigarette smoking, it is of critical importance to keep the dose of nicotine as constant as possible. This is difficult with smoking, because when the nicotine delivery of a cigarette is increased or reduced, smokers tend to compensate by modifying their smoke intake. In a laboratory study, it is relatively easy to control the number of cigarettes and the number of puffs taken, but it is more difficult to control the volume of each puff. Various procedures have been developed to control puff volume, but they have a disadvantage of disrupting the normal topography of smoking. We have developed an apparatus for delivering fixed volumes of smoke that has given consistent tar and nicotine values needed in studies of the behavioral and physiological effects of cigarette smoking. This method has the distinct advantage of allowing the subject to inhale the smoke in a normal fashion, with a draw resistance comparable to that of a cigarette. The device is inexpensive and easy to make. © 1989 Psychonomic Society, Inc.

Authors
Levin, ED; Rose, JE; Behm, F
MLA Citation
Levin, ED, Rose, JE, and Behm, F. "Controlling puff volume without disrupting smoking topography." Behavior Research Methods, Instruments, & Computers 21.3 (1989): 383-386.
Source
scival
Published In
Behavior research methods, instruments, & computers : a journal of the Psychonomic Society, Inc
Volume
21
Issue
3
Publish Date
1989
Start Page
383
End Page
386
DOI
10.3758/BF03202801

A noninvasive method for delivering controlled doses of nicotine via cigarette smoke

A cigarette-smoke delivery system is described in which nicotine dosage was delimited by having the subject inhale a measured amount of smoke to a predetermined depth and duration of inhalation. A plastic syringe was used to "inject" a specified amount of cigarette smoke into the subject's mouth, and an airbag containing 1 liter of air was used to provide a "chaser" with a fixed volume of inhalation for the smoke. Using plasma nicotine boost as an indicator, dose control was found to be nearly linear for the three dose levels employed; in the high-dose condition, plasma nicotine levels were moderately consistent within subjects over three successive administrations. Between-subject variability was considerably greater than within-subject variability, however, suggesting that each smoker obtained a characteristic nicotine boost that reflected individual differences in nicotine pharmacokinetics in addition to nicotine intake per se. © 1989 Psychonomic Society, Inc.

Authors
Pomerleau, OF; Rose, JE; Pomerleau, CS; Majchrzak, MJ
MLA Citation
Pomerleau, OF, Rose, JE, Pomerleau, CS, and Majchrzak, MJ. "A noninvasive method for delivering controlled doses of nicotine via cigarette smoke." Behavior Research Methods, Instruments, & Computers 21.6 (1989): 598-602.
Source
scival
Published In
Behavior research methods, instruments, & computers : a journal of the Psychonomic Society, Inc
Volume
21
Issue
6
Publish Date
1989
Start Page
598
End Page
602
DOI
10.3758/BF03210582

Methodological review. Controlled dosing of nicotine: A review of problems and progress

Authors
Pomerleau, OF; Pomerleau, CS; Rose, JE
MLA Citation
Pomerleau, OF, Pomerleau, CS, and Rose, JE. "Methodological review. Controlled dosing of nicotine: A review of problems and progress." Annals of Behavioral Medicine 11.4 (1989): 158-162.
Source
scival
Published In
Annals of Behavioral Medicine
Volume
11
Issue
4
Publish Date
1989
Start Page
158
End Page
162

Effects of controlled nicotine doses upon punished and non-punished responding in humans

Authors
Bennett, RH; Cherek, DR; Roache, JD; Rose, JE
MLA Citation
Bennett, RH, Cherek, DR, Roache, JD, and Rose, JE. "Effects of controlled nicotine doses upon punished and non-punished responding in humans." NIDA Research Monograph Series 95 (1989): 438-439.
PMID
2641021
Source
scival
Published In
NIDA Research Monograph Series
Issue
95
Publish Date
1989
Start Page
438
End Page
439

Effect of naloxone on cigarette smoking

Several recent studies have tried to link endogenous opioid peptides (endorphins) with smoking reinforcement. Karras and Kane (1980) showed a one-third decrease in smoking after administration of the opiate antagonist naloxone. However, Nemeth-Coslett and Griffiths (1986) failed to replicate this result with use of a wide range of doses. The current study was an attempt to replicate Karras and Kane's results using 10 male chronic smokers. Each subject received naloxone (10 mg sc) or placebo in a double-blind, cross-over design (cross-over interval 6-14 days) after overnight abstinence from tobacco use. Naloxone reduced the number of cigarettes smoked by 16% in the first 1/2 hour smoking period, with a 10% reduction in carbon monoxide level 1 hour later. Naloxone had no effect on subjective and physiological variables and did not cause any signs of a tobacco withdrawal syndrome. These results are consistent with those of Karras and Kane, and suggest a role for endorphins in smoking reinforcement. Inconsistent results across studies may be due to methodological factors, such as differences in smoking deprivation time and postnaloxone administration testing intervals because naloxone has a short half-life. © 1989 Ablex Publishing Corporation.

Authors
Gorelick, DA; Rose, J; Jarvik, ME
MLA Citation
Gorelick, DA, Rose, J, and Jarvik, ME. "Effect of naloxone on cigarette smoking." Journal of Substance Abuse 1.2 (1988): 153-159.
PMID
2980866
Source
scival
Published In
Journal of Substance Abuse
Volume
1
Issue
2
Publish Date
1988
Start Page
153
End Page
159

The effect of nicotine on the delay of gastric emptying.

The effect of cigarette smoking and its active component, nicotine, on the gastric emptying of solid food was assessed in a randomized double-blind crossover design. Ten regular smokers were studied after a 6 h fast and least 18 h after their last cigarette. Subjects smoked a total of three high (1.91 mg) or low (0.17 mg) nicotine cigarettes, before and after a technetium-labelled solid meal and were scanned by gamma camera periodically over a 2-h period. All calculations of gastric emptying revealed a significant delay after smoking high versus low nicotine cigarettes in: mean per cent isotope remaining in the stomach at each measurement point from 90-120 min; amount of meal remaining in the stomach at 2 h; and mean time at which 50% of the meal had emptied (T1/2). Delay in gastric emptying was significantly correlated with increase in serum nicotine concentration on the high nicotine day.

Authors
Gritz, ER; Ippoliti, A; Jarvik, ME; Rose, JE; Shiffman, S; Harrison, A; Vunakis, HV
MLA Citation
Gritz, ER, Ippoliti, A, Jarvik, ME, Rose, JE, Shiffman, S, Harrison, A, and Vunakis, HV. "The effect of nicotine on the delay of gastric emptying." Alimentary Pharmacology and Therapeutics 2.2 (1988): 173-178.
PMID
2979243
Source
scival
Published In
Alimentary Pharmacology and Therapeutics
Volume
2
Issue
2
Publish Date
1988
Start Page
173
End Page
178

Pulmonary hazards of smoking marijuana as compared with tobacco

To compare the pulmonary hazards of smoking marijuana and tobacco, we quantified the relative burden to the lung of insoluble particulates (tar) and carbon monoxide from the smoke of similar quantities of marijuana and tobacco. The 15 subjects, all men, had smoked both marijuana and tobacco habitually for at least five years. We measured each subject's blood carboxyhemoglobin level before and after smoking and the amount of tar inhaled and deposited in the respiratory tract from the smoke of single filter-tipped tobacco cigarettes (900 to 1200 mg) and marijuana cigarettes (741 to 985 mg) containing 0.004 percent or 1.24 percent Δ9-tetrahydrocannabinol. As compared with smoking tobacco, smoking marijuana was associated with a nearly fivefold greater increment in the blood carboxyhemoglobin level, an approximately threefold increase in the amount of tar inhaled, and retention in the respiratory tract of one third more inhaled tar (P < 0.001). Significant differences were also noted in the dynamics of smoking marijuana and tobacco, among them an approximately two-thirds larger puff volume, a one-third greater depth of inhalation, and a fourfold longer breath-holding time with marijuana than with tobacco (P < 0.01). Smoking dynamics and the delivery of tar during marijuana smoking were only slightly influenced by the percentage of tetrahydrocannabinol. We conclude that smoking marijuana, regardless of tetrahydrocannabinol content, results in a substantially greater respiratory burden of carbon monoxide and tar than smoking a similar quantity of tobacco.

Authors
Wu, T-C; Tashkin, DP; Dhahed, B; Rose, JE
MLA Citation
Wu, T-C, Tashkin, DP, Dhahed, B, and Rose, JE. "Pulmonary hazards of smoking marijuana as compared with tobacco." New England Journal of Medicine 318.6 (1988): 347-351.
PMID
3340105
Source
scival
Published In
New England Journal of Medicine
Volume
318
Issue
6
Publish Date
1988
Start Page
347
End Page
351

Influence of marijuana potency and amount of cigarette consumed on marijuana smoking pattern

The authors of the present article continuously monitored - in a single-blind fashion - the smoking patterns (topography) of experienced marijuana users while they smoked marijuana cigarettes of two different potencies: 0.004 percent THC (placebo) and 1.24 percent THC. In 15 habitual users of marijuana, a significantly smaller puff volume during the smoking of the second half compared to the first half of a marijuana cigarette was observed. The present findings that the dynamics of smoking marijuana cigarettes of different potency were similar within individuals despite significantly different perceived levels of intoxication do not support the hypothesis that less potent marijuana cigarettes are smoked less aggressively.

Authors
Wu, T-C; Tashkin, DP; Rose, JE; Djahed, B
MLA Citation
Wu, T-C, Tashkin, DP, Rose, JE, and Djahed, B. "Influence of marijuana potency and amount of cigarette consumed on marijuana smoking pattern." Journal of Psychoactive Drugs 20.1 (1988): 43-46.
PMID
2839655
Source
scival
Published In
Journal of Psychoactive Drugs
Volume
20
Issue
1
Publish Date
1988
Start Page
43
End Page
46

Noninvasive measurement of smokers' tar and nicotine intake

A simple device for monitoring cigarette smokers' intake of tar and nicotine is described. This device divided the mainstream smoke into two parallel paths, one containing seven parallel capillary tubes and the other containing one capillary tube; a Cambridge filter trapped the smoke passing through the path containing one tube. Analyses of both tar and nicotine trapped in the filter were performed by gravimetric and chemical methods. Calibration tests verified that a constant fraction of the tar and nicotine was retained in the apparatus over a wide range of conditions, allowing the calculation of smoke intake into the mouth. With supplementary methods for measuring the amount of smoke exhaled, the apparatus can be used to measure smoke deposition in the respiratory tract. © 1987 Psychonomic Society, Inc.

Authors
Rose, JE; Wu, T-C; Djahed, B; Tashkin, DP
MLA Citation
Rose, JE, Wu, T-C, Djahed, B, and Tashkin, DP. "Noninvasive measurement of smokers' tar and nicotine intake." Behavior Research Methods, Instruments, & Computers 19.3 (1987): 295-299.
Source
scival
Published In
Behavior research methods, instruments, & computers : a journal of the Psychonomic Society, Inc
Volume
19
Issue
3
Publish Date
1987
Start Page
295
End Page
299
DOI
10.3758/BF03202564

Citric acid aerosols as a potential smoking cessation aid

We tested the ability of a citric acid aerosol to stimulate the tracheal sensations produced by cigarette smoke and to satisfy smokers' desire for cigarettes. Fifteen smokers rated puffs from their own brand of cigarette, citric acid aerosol, a low tar and nicotine cigarette, and air. To focus on tracheal perceptions and pharmacologic effects of nicotine, we equated visual, olfactory and taste cues across conditions. Subjects rated the citric acid aerosol more similar to their own brand, more desirable, and more satisfying (after a block of puffs) than control puffs of air. It was also rated equal to or better than the low tar and nicotine cigarette. Subjects' own brands were rated best, although puffs of citric acid aerosol were of comparable strength and harshness. The results suggest that a nebulizer delivering citric acid in a fine mist might reduce craving for cigarettes in smokers attempting to quit and may thereby increase cessation rates.

Authors
Rose, JE; Hickman, CS
MLA Citation
Rose, JE, and Hickman, CS. "Citric acid aerosols as a potential smoking cessation aid." Chest 92.6 (1987): 1005-1008.
PMID
3677804
Source
scival
Published In
Chest
Volume
92
Issue
6
Publish Date
1987
Start Page
1005
End Page
1008

Refined cigarette smoke as a method for reducing nicotine intake

We developed a method of refining tobacco smoke to deliver sensory components of cigarette smoking while minimizing the delivery of nicotine and other toxic smoke constituents. In the first experiment, smokers rated puffs of their own brands of cigarette, a commercial low tar and nicotine cigarette, and refined smoke. The refined smoke was rated significantly stronger and more desirable than the low tar and nicotine cigarette despite a comparably low nicotine delivery; subjects' own brands were rated best, but in standardized smoking tests delivered over ten times more tar, nicotine and carbon monoxide. In the second experiment, subjects smoked five times on each of two mornings; one day they received refined smoke and the other day smoked a low tar and nicotine cigarette. The refined smoke produced significantly more satisfaction, yet delivered far less carbon monoxide and tar (assessed by mouth intake). Nicotine intake was comparable to that of the low tar and nicotine cigarette. Because refined smoke substantially reduced subjects' craving for cigarettes while reducing nicotine intake, it may prove to be a useful short-term adjunct to a smoking cessation program. Additionally, the method may be useful in research analyzing the relative contributions of pharmacologic actions of inhaled smoke and the sensory cues associated with nicotine intake as reinforcers maintaining smoking behavior. © 1987.

Authors
Rose, JE; Behm, F
MLA Citation
Rose, JE, and Behm, F. "Refined cigarette smoke as a method for reducing nicotine intake." Pharmacology, Biochemistry and Behavior 28.2 (1987): 305-310.
PMID
3685063
Source
scival
Published In
Pharmacology Biochemistry and Behavior
Volume
28
Issue
2
Publish Date
1987
Start Page
305
End Page
310

Cigarette smoking blocks caffeine-induced arousal

The interactive effects of caffeine and cigarette smoking were studied in fifteen subjects. Four experimental sessions presented either decaffeinated coffee or caffeinated coffee (containing 150 mg caffeine base), followed 20 min later by a smoking or nonsmoking period (20 min duration). Puffing behavior and end-expired air carbon monoxide concentrations were measured to estimate smoke intake. Subjective reports of arousal and tension, and physiologic measures of heart rate and blood pressure were collected. Subjective arousal showed a highly significant antagonistic interaction between caffeine and smoking; smoking blocked the subjective stimulant effects of caffeine. The only cardiovascular effect noted was an increase in heart rate after smoking. Caffeine did not significantly influence puffing behavior; however, the increase in end-expired carbon monoxide concentration, after smoking was greater in the caffeine condition, suggesting subjects inhaled more smoke after caffeinated than decaffeinated coffee.

Authors
Rose, JE
MLA Citation
Rose, JE. "Cigarette smoking blocks caffeine-induced arousal." Alcohol and Drug Research 7.1 (1987): 49-55.
PMID
3790213
Source
scival
Published In
Alcohol and Drug Research
Volume
7
Issue
1
Publish Date
1987
Start Page
49
End Page
55

Cigarette desirability and nicotine preference in smokers

We conducted two experiments to explore the role of nicotine in the maintenance of cigarette smoking behavior. In Experiment 1 we determined that, compared to 0 or 2 mg injections, an injection of 4 mg nicotine base into the filter of non-nicotine cigarettes significantly increased their desirability. In Experiment 2, to determine how nicotine-seeking varied across a wide range of cigarette deprivation, we studied nicotine preference under three cigarette deprivation conditions: overnight abstinence, 30 min deprivation, and immediately after smoking (satiation condition). Nicotine preference was assessed by allowing subjects to freely adjust the nicotine concentration of each puff using a smoke mixing device. Nicotine preference was greatest after overnight deprivation. Least after satiation, and intermediate after 30 min deprivation. However, nicotine seeking increased as a function of cigarette deprivation despite the fact that higher nicotine puffs were rated as harsher, stronger and less desirable than lower nicotine puffs. The results of both experiments suggest an inverted-U relationship between nicotine content and desirability. © 1986.

Authors
Herskovic, JE; Rose, JE; Jarvik, ME
MLA Citation
Herskovic, JE, Rose, JE, and Jarvik, ME. "Cigarette desirability and nicotine preference in smokers." Pharmacology, Biochemistry and Behavior 24.2 (1986): 171-175.
PMID
3952107
Source
scival
Published In
Pharmacology Biochemistry and Behavior
Volume
24
Issue
2
Publish Date
1986
Start Page
171
End Page
175

Sensory blockade of smoking satisfaction

Cigarette smokers were presented with controlled doses of cigarette smoke to determine wheter the resulting reduction in cigarette craving depended upon perceiving the sensory qualities of the smoke. Cigarette craving was assessed before and after inhaling controlled doses of smoke in two conditions: (1) Local anesthesia of the upper and lower respiratory airways, induced by mouth rinsing, gargling and inhalation of a mist containing the topical anesthetic lidocaine; and (2) no-anesthesia control, in which all solutions were saline. A sham smoking procedure was presented in both conditions. Craving and ad lib smoking behavior were also assessed 30 minutes after controlled smoking. The results indicated that smoke, as opposed to sham puffs, significantly reduced reports of cigarette craving, and local anesthesia significantly blocked this immediate reduction in craving produced by smoke inhalation. Puffs were also rated as less desirable in the anesthesia condition. Thirty minutes after smoking, craving was no different in the anesthesia and saline control conditions. However, craving as well as smoking intake in both conditions was less when smoke had been given previously than in the sham smoking control. These results suggest that sensory cues accompanying inhalation of cigarette smoke are important determinants of immediate smoking satisfaction. However, the sustained effects of smoke intake on subsequent smoking behavior (30 min later) may be mediated by processes other than sensory stimulation of the respiratory tract, such as plasma nicotine levels. © 1985.

Authors
Rose, JE; Tashkin, DP; Ertle, A; Zinser, MC; Lafer, R
MLA Citation
Rose, JE, Tashkin, DP, Ertle, A, Zinser, MC, and Lafer, R. "Sensory blockade of smoking satisfaction." Pharmacology, Biochemistry and Behavior 23.2 (1985): 289-293.
PMID
4059314
Source
scival
Published In
Pharmacology Biochemistry and Behavior
Volume
23
Issue
2
Publish Date
1985
Start Page
289
End Page
293

Alcohol increases cigarette smoking: A laboratory demonstration

Most people would agree that a relationship exists between drinking alcohol and smoking cigarettes, but there is very little empirical evidence demonstrating a direct causal association. Study of the relationship has been hampered by the lack of a simple laboratory methodology. This article describes an efficient experimental paradigm. Fourteen male narcotic addicts in methadone maintenance treatment volunteered to come to the laboratory for two smoking sessions, during which each subject was given either an alcoholic drink or orange juice, followed by three cigarettes at 20-minute intervals. Drinking alcohol significantly increased the amount and rate of smoking. However, not all subjects reacted to alcohol with increased smoking, and we were unable to account for those individual differences. Our finding supports the theory that a direct causal mechanism linking smoking and drinking exists. That link probably has clinical significance, because there is evidence that ex-smokers are at particularly high risk when they drink alcohol. © 1985.

Authors
Mintz, J; Boyd, G; Rose, JE; Charuvastra, VC; Jarvik, ME
MLA Citation
Mintz, J, Boyd, G, Rose, JE, Charuvastra, VC, and Jarvik, ME. "Alcohol increases cigarette smoking: A laboratory demonstration." Addictive Behaviors 10.3 (1985): 203-207.
PMID
4083099
Source
scival
Published In
Addictive Behaviors
Volume
10
Issue
3
Publish Date
1985
Start Page
203
End Page
207

Transdermal nicotine reduces cigarette craving and nicotine preference

The effects of transdermal nicotine in 10 cigarette smokers were studied in a within-subjects, doubleblind design. Either 8 mg nicotine base in a 30% aqueous solution or an inactive placebo solution was applied to intact skin under a polyethylene patch. Subjective reports of cigarette craving were collected every 30 minutes during a 90-minute smoking abstinence period. Immediately before and after this abstinence period subjects smoked through a smoke mixing device that allowed them to select their desired nicotine intake with each puff. Transdermal nicotine significantly increased saliva nicotine levels within 30 minutes after application. Cigarette craving was significantly lower in the nicotine condition than in the placebo condition. Nicotine preference during the initial puffs of the smoke mixer test at the end of 90 minutes of deprivation was also decreased by transdermal nicotine. In contrast, measures of cumulative smoke intake were not affected by the nicotine dose used. Our results suggest that transdermal nicotine may enhance success in smoking cessation by preventing the rise in cigarette craving usually observed after cessation. Transdermal nicotine may be preferable to other routes of nicotine administration because of the relative absence of adverse side effects. © 1985.

Authors
Rose, JE; Herskovic, JE; Trilling, Y; Jarvik, ME
MLA Citation
Rose, JE, Herskovic, JE, Trilling, Y, and Jarvik, ME. "Transdermal nicotine reduces cigarette craving and nicotine preference." Clinical Pharmacology and Therapeutics 38.4 (1985): 450-456.
PMID
4042528
Source
scival
Published In
Clinical Pharmacology & Therapeutics (Nature)
Volume
38
Issue
4
Publish Date
1985
Start Page
450
End Page
456

Nicotine preference increases after cigarette deprivation

In order to test the theory that nicotine is a reinforcing constituent in tobacco, smokers' nicotine preference was assessed after two hours' cigarette deprivation and immediately after smoking two cigarettes. Preference was measured by allowing subjects to freely adjust the nicotine concentration of each puff using a smoke mixing device. Nicotine preference was significantly higher after deprivation, showing that nicotine in cigarette smoke is positively reinforcing and smokers' attempts to obtain nicotine vary with prior cigarette consumption. © 1984.

Authors
Rose, JE; Jarvik, ME; Ananda, S
MLA Citation
Rose, JE, Jarvik, ME, and Ananda, S. "Nicotine preference increases after cigarette deprivation." Pharmacology, Biochemistry and Behavior 20.1 (1984): 55-58.
PMID
6695000
Source
scival
Published In
Pharmacology Biochemistry and Behavior
Volume
20
Issue
1
Publish Date
1984
Start Page
55
End Page
58
DOI
10.1016/0091-3057(84)90100-X

Transdermal administration of nicotine

The physiological response to nicotine topically applied to the skin was measured in an adult male volunteer. Nicotine base (9 mg) was applied in a 30% aqueous solution to intact skin on the underside of the forearm. Salivary nicotine, heart rate and blood pressure were monitored for 12 h after application of the nicotine. Within 30 min a significant level of nicotine was detected in the saliva (50 ng/ml), pulse had risen by 15 beats/min and systolic blood pressure had risen 10 mmHg. Nicotine levels remained elevated for 2 h and were comparable to levels of nicotine produced by cigarette smoking. Because previous research has shown nicotine to suppress smoking behavior, it may be fruitful to examine transdermal administration of nicotine as a smoking reduction and cessation aid. © 1984.

Authors
Rose, JE; Jarvik, ME; Rose, KD
MLA Citation
Rose, JE, Jarvik, ME, and Rose, KD. "Transdermal administration of nicotine." Drug and Alcohol Dependence 13.3 (1984): 209-213.
PMID
6734425
Source
scival
Published In
Drug and Alcohol Dependence
Volume
13
Issue
3
Publish Date
1984
Start Page
209
End Page
213

Subjective response to cigarette smoking following airway anesthetization

Subjective response to cigarette smoking was assessed after partial blockade of upper and lower airway sensations by the topical application of lidocaine. Pack-a-day smokers were given one cigarette after each of four conditions: (1) mouth anesthesia, obtained by rinsing the mouth with 2% lidocaine; (2) mouth and pharyngeal anesthesia, in which subjects rinsed their mouths and gargled with 2% lidocaine; (3) upper and lower airway anesthesia, in which subjects rinsed their mouths and gargled with a 2% lidocaine solution, and inhaled a mist containing 4% lidocaine (60 breaths); and (4) saline control, in which all solutions (rinse, gargle and inhalation) were saline. A significant linear decline in cigarette craving occured with increasing anesthesia, and desirability ratings over the first several puffs were also reduced by anesthesia. These results suggest that sensory cues are important factors in smoking satisfaction, and their influence can be analyzed with the use of local anesthetics. © 1984.

Authors
Rose, JE; Zinser, MC; Tashkin, DP; Newcomb, R; Ertle, A
MLA Citation
Rose, JE, Zinser, MC, Tashkin, DP, Newcomb, R, and Ertle, A. "Subjective response to cigarette smoking following airway anesthetization." Addictive Behaviors 9.2 (1984): 211-215.
PMID
6741683
Source
scival
Published In
Addictive Behaviors
Volume
9
Issue
2
Publish Date
1984
Start Page
211
End Page
215

Discriminability of nicotine in tobacco smoke: Implications for titration

Cigarette smokers were presented with puffs from either high (2.5 mg), medium (1.5 mg) or low (.5 mg) nicotine cigarettes in order to determine their ability to discriminate nicotine delivery in tobacco smoke. Puffs were presented in random order during each of two conditions and tar content was controlled by using research cigarettes and a smoke mixing device that varied only nicotine. The first condition allowed olfactory stimuli to be used in discrimination, while the second condition blocked olfaction by occluding subjects' nostrils. In both conditions, subjects discriminated between the nicotine content of different puffs, with higher nicotine puffs rated as significantly stronger (by roughly 50%). Subjective desirability ratings did not vary with nicotine delivery. The implications of the magnitude of change in subjects' ratings for theories of nicotine titration are discussed. © 1984.

Authors
Rose, JE
MLA Citation
Rose, JE. "Discriminability of nicotine in tobacco smoke: Implications for titration." Addictive Behaviors 9.2 (1984): 189-193.
PMID
6741679
Source
scival
Published In
Addictive Behaviors
Volume
9
Issue
2
Publish Date
1984
Start Page
189
End Page
193
DOI
10.1016/0306-4603(84)90056-X

Cigarette smoking during anxiety-provoking and monotonous tasks

Cigarette smokers were exposed to three conditions within a single session: stagefright anxiety, monotonous concentration, and a relaxation control. One cigarette was lit during the second 10-minute half of each condition, and smoking topography (number of puffs and cumulative volume smoked) was continuously recorded. Subjects smoked significantly more in the two task conditions than during relaxation, supporting the hypothesis that anxiety-provoking and attention-demanding situations elicit smoking. Younger subjects increased their smoking more than older subjects during stagefright, and females responded more than males to the concentration task. © 1984.

Authors
Rose, JE; Ananda, S; Jarvik, ME
MLA Citation
Rose, JE, Ananda, S, and Jarvik, ME. "Cigarette smoking during anxiety-provoking and monotonous tasks." Addictive Behaviors 8.4 (1983): 353-359.
PMID
6677075
Source
scival
Published In
Addictive Behaviors
Volume
8
Issue
4
Publish Date
1983
Start Page
353
End Page
359
DOI
10.1016/0306-4603(83)90035-7

Cigarette smoking behavior in conjoined twins

Authors
Jarvik, ME; Gritz, ER; Rose, JE
MLA Citation
Jarvik, ME, Gritz, ER, and Rose, JE. "Cigarette smoking behavior in conjoined twins." Acta Geneticae Medicae et Gemellologiae 32.3-4 (1983): 239-243.
PMID
6673459
Source
scival
Published In
Acta Geneticae Medicae et Gemellologiae
Volume
32
Issue
3-4
Publish Date
1983
Start Page
239
End Page
243

Analysis of reinforcement by varying smoke component concentrationa

Since nicotine is thought to be one of the principal reinforcing constituents in tobacco, a logical way to classify smokers may be to distinguish those who are dependent on nicotine from those who smoke for other reasons, e.g., other components of tobacco, sensory/motor aspects of the habit, or social reasons. The methodology described here was designed to study the reinforcing actions of nicotine in smokers in a way that would overcome two conceptual problems inherent in most nicotine titration studies. The first problem is that if nicotine is a reinforcer for smoking, smokers would not be expected to like low-nicotine cigarettes. The second problem is that even if titration does occur, it would be consistent with the view that nicotine is aversive rather than reinforcing and that smokers are obtaining other reinforcers from the cigarette. The new methodology to be described here explores variations in nicotine preference in which the concentration of nicotine in each puff of smoke is under the subject's control. In this choice procedure, subjects utilize a smoke-mixing apparatus to adjust the nicotine concentration in cigarette smoke on a puff-by-puff basis and select an optimal nicotine delivery. The rewarding and/or aversive properties of nicotine at a specific time can be inferred by the nicotine level chosen.

Authors
Rose, JE
MLA Citation
Rose, JE. "Analysis of reinforcement by varying smoke component concentrationa." NIDA Research Monograph Series NO. 48 (1983): 39-49.
PMID
6443143
Source
scival
Published In
NIDA Research Monograph Series
Volume
NO. 48
Publish Date
1983
Start Page
39
End Page
49

Regulation of tobacco smoke intake with paced cigarette presentation

Smoking behavior in response to an increased presentation of cigarettes was investigated to determine whether compensatory changes occurred in order to maintain a constant intake of tobacco smoke. The lighting of each cigarette was paced at both twice and four times that of subjects' baseline smoking rates in a three condition repeated measures design for eight smokers. Puff topography-number of puffs per cigarette, puff duration, volume, peak flow and interpuff interval-was monitored continuously. Results showed that subjects titrated smoke intake, as summarized by three smoke compensation indices based on number of puffs, puff volume and puff duration. Compensation was virtually complete in the double rate condition, and substantial in the quadruple rate condition. Results of this experiment do not support the view of a bimodal distribution of smokers, "compensators" and "noncompensators," since a continuous range of compensation ratios was obtained. The measures of individual puff topography were only modestly correlated, and were generally highest for volume × duration. Volume would appear to be the most accurate measure of tobacco product consumed. © 1983.

Authors
Gritz, ER; Rose, JE; Jarvik, ME
MLA Citation
Gritz, ER, Rose, JE, and Jarvik, ME. "Regulation of tobacco smoke intake with paced cigarette presentation." Pharmacology, Biochemistry and Behavior 18.3 (1983): 457-462.
PMID
6836000
Source
scival
Published In
Pharmacology Biochemistry and Behavior
Volume
18
Issue
3
Publish Date
1983
Start Page
457
End Page
462

A smoke-mixing device for measuring nicotine preference

A smoke-mixing device is described that allows individuals to select their preferred nicotine deliveries from cigarette smoke on a puff-by-puff basis. This methodology offers advantages over previous strategies to investigate the role of nicotine as a reinforcing constituent of tobacco. © 1982 Psychonomic Society, Inc.

Authors
Rose, JE; Lafer, RL; Jarvik, ME
MLA Citation
Rose, JE, Lafer, RL, and Jarvik, ME. "A smoke-mixing device for measuring nicotine preference." Behavior Research Methods & Instrumentation 14.6 (1982): 501-503.
Source
scival
Published In
Behavior Research Methods
Volume
14
Issue
6
Publish Date
1982
Start Page
501
End Page
503
DOI
10.3758/BF03203412

Self-punitive behavior in humans: Effects of a self-fulfilling prophecy

Human subjects were exposed to contingencies which programmed aversive tones (100 db). Two types of contingencies were employed: self-confirming (i.e., self-fulfilling prophecies), in which the aversive tone was occasioned by the prediction it was about to occur; and self-disconfirming, in which the tone was probable when subjects predicted it would not occur. Experiments 1 and 2 used a modified classical conditioning paradigm, and demonstrated that a self-confirming contingency maintained reliable self-punitive responding, i.e., subjects consistently predicted and therefore obtained tones on every trial. Subjects in Experiment 3 were instructed to express predictions continuously throughout four sessions to ensure adequate sampling of the various predictions. Subjects exposed to a self-disconfirming contnngency reliably evidenced awareness of the contingency in effect (judged by answers on a postexperimental questionnaire), whereas subjects exposed to a self-confirming contingency failed to show effective avoidance behavior or contingency awareness. Experiment 4 investigated free-operant self-punitive behavior, utilizing a single prediction response button, which subjects depressed repeatedly. Subjects were exposed to either periodic or aperiodic punishment schedules over as many as four sessions. In general, more persistent self-punitive responding was found in the groups receiving periodic punishment. The results from the four experiments show that self-confirming contingencies can effectively prolong self-punitive responding in human subjects. The findings are consistent with a blocking interpretation of self-punitive behavior, which asserts that when an aversive event is already predicted by stimuli in the situation (including temporal cues), the association between a response and punishment is impaired, and self-punitive responding is likely to be maintained. An integration of human and animal self-punitive research is proposed. © 1981.

Authors
Rose, JE; Fantino, E
MLA Citation
Rose, JE, and Fantino, E. "Self-punitive behavior in humans: Effects of a self-fulfilling prophecy." Learning and Motivation 12.2 (1981): 212-238.
Source
scival
Published In
Learning and Motivation
Volume
12
Issue
2
Publish Date
1981
Start Page
212
End Page
238
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