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Smoking induced dopamine release: buproprion effects

Institution: Brentwood Biomedical Research Institute
Investigator(s): Arthur Brody, M.D.
Award Cycle: 2002 (Cycle 11) Grant #: 11RT-0024 Award: $659,060
Subject Area: Nicotine Dependence
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Despite new medications for the treatment of addiction to cigarettes, abstinence rates after 1 year of treatment remain relatively low (about 1/4 success rate). Bupropion is one of the few medications that has proven to be superior to placebo (inactive pills) in helping smokers maintain abstinence and in reducing craving for cigarettes. We propose to study how bupropion works in human cigarette smokers. The purpose of this study is to determine if a course of treatment with bupropion attenuates the brain concentration of a chemical called dopamine that gets released when smokers smoke a cigarette. A better understanding of the mechanisms of action of current treatments, such as bupropion, may advance the development of more effective treatments for cigarette smoking.

Bupropion has many effects on the brain, including increasing the amount of free dopamine. It has been shown in animals and in a small group of humans studied by our group that dopamine gets released in the brain in response to nicotine administration and cigarette smoking. We will use a type of brain imaging called positron emission tomography (or PET) scanning to examine smoking-induced dopamine release before and after treatment with bupropion. While we presume that cigarette smoking does lead to dopamine release in smokers when they smoke a cigarette, the effect of treatment with bupropion on smoking-induced dopamine release has not yet been reported.

The central aim of the study is to determine the effect of treatment with bupropion (compared with an inactive pill placebo) on smoking-induced increases in dopamine levels in the brain. We predict that subjects treated with bupropion will have greater attenuation of smoking-induced increases in dopamine than placebo-treated subjects (from before to after treatment). Other goals of the study include the examination of changes in resting dopamine levels from before to after treatment with bupropion and associations between dopamine release and clinical effects of cigarette smoking (such as decreases in craving and nervousness, and increases in euphoria). We will also determine if we can predict who will quit smoking with bupropion based on smoking-induced increases in brain dopamine before.

Heavy smokers (who smoke at least 15 cigarettes per day) who are addicted to cigarettes will have PET scanning sessions using a new type of brain imaging that examines dopamine levels in the brain. Subjects will smoke during the PET scans using a special cigarette smoke delivery system (a hookah) that was designed by our group for use in brain imaging studies. Subjects will be randomly assigned to be treated with either bupropion or an inactive pill placebo and will have a PET session before and after a standard course of treatment for 4 weeks to determine changes in brain dopamine concentration in response to smoking. Because some subjects will be assigned to an inactive treatment, all subjects will be offered a free course of active treatment after they complete the study.
Publications

Brain metabolic changes during cigarette craving.
Periodical: Archives of General Psychiatry Index Medicus:
Authors: Brody AL, Mandelkern MA, London ED, Childress AR, Lee GS, Bota RG, Ho ML, Saxena S, et al. ART
Yr: 2002 Vol: 59 Nbr: Abs: Pg: 1162-1172

Differences between smokers and non-smokers in regional gray matter volumes and densities.
Periodical: Biological Psychiatry Index Medicus:
Authors: Brody AL, Mandelkern MA, Jarvik ME, Lee GS, Smith EC, Huang JC, Bota RG, Bartzokis G,et al ART
Yr: 2004 Vol: 55 Nbr: 1 Abs: Pg: 77-84

Smoking-induced ventral striatal dopamine release.
Periodical: American Journal of Psychiatry Index Medicus:
Authors: Brody AL, Olmstead RE, London ED, Farahi J, Meyer JH, Grossman P, Lee GS, Huang J, et al. ART
Yr: 0 Vol: Nbr: Abs: Pg:

Attenuation of cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study.
Periodical: Psychiatry Research Neuroimaging Index Medicus:
Authors: Brody AL, Mandelkern MA, Lee G, Smith E, Sadeghi M, Saxena S, Jarvik MA, London ED ART
Yr: 0 Vol: Nbr: Abs: Pg:

Smoking-induced ventral striatal dopamine release.
Periodical: American College of Neuropsychopharmacology: Scientific Abstracts Index Medicus:
Authors: Brody AL, Olmstead RE, Mandelkern MA, Lee GS, Huang J, Hahn E, London ED ABS
Yr: 2003 Vol: Nbr: Abs: Pg:

Brain dopamine release induced by cigarette smoking.
Periodical: Society for Research on Nicotine and Tobacco Conference Index Medicus:
Authors: Brody AL, Olmstead RE< London ED, Mandelkern MA ABS
Yr: 2004 Vol: Nbr: Abs: Pg:

Brain Activity in Cigarette Smoker Performing a Working Memory Task: Effect of Smoking Abstinence.
Periodical: Biological Psychiatry Index Medicus:
Authors: Xu J, Mendrek A, Cohen MS, Monterosso J, Rodriguez P, Simon S, Brody AL, Jarvik ME ART
Yr: 2005 Vol: 58 Nbr: Abs: Pg: 143-150

Common Substrates of Dysphoria in Psychostimulant Abuse and Primary Depression
Periodical: International Review of Neurobiology Index Medicus:
Authors: Baicy K, Bearden C, Monterosso J, Brody AL , London ED ART
Yr: 2005 Vol: 65 Nbr: Abs: Pg: 117-145

Functional Brain Imaging of Tobacco Use and Dependence
Periodical: Journal of Psychiatric Research Index Medicus:
Authors: Brody AL ART
Yr: 2006 Vol: 40 Nbr: Abs: Pg: 404-418

Working Memory in Cigarette Smokers: Comparison to NO-Smokers abd Effects of Abstinence
Periodical: Addictive Behaviors Index Medicus:
Authors: Mendrek A, Monterosso J, Simon SL, Jarvik M, Brody AL, Olmstead RE, Domier CP, Cohen ART
Yr: 2006 Vol: 31 Nbr: Abs: Pg: 833-844

Genetic Variants of the Dopamine Transporter, DRD4 and COMT predict smoking-Induced dopamine release
Periodical: Archives of General Psychiatry Index Medicus:
Authors: Brody AL, Mandelkern MA, London ED, Olmstead RE, Farahi J, Scheibal D, Jou J, Allen V ART
Yr: 2006 Vol: 63 Nbr: Abs: Pg: 808-816

Cigarette Smoking Saturates a4B2 Nicotinic Acetylcholine Repceptors
Periodical: Archives of General Psychiatry Index Medicus:
Authors: Brody Al, Mandelkern MA, London ED, Olmstead RE, Farahi J, Scheibal D, Jou J, Allen V ART
Yr: 2006 Vol: 63 Nbr: Abs: Pg: 907-915

Effects of acute smoking on brain activity vary with abstinece in smoking performing the n-back task a preliminary Study
Periodical: Psychiatry Research Neuroimaging Index Medicus:
Authors: Xu J, Mendrek A, Cohen MS, Monterosso JR, Simon SL, Brody AL, Jarvik ME, Rodriguez P ART
Yr: 2006 Vol: Nbr: Abs: Pg:

Effects of Cigarette Smoking on Prefrontal Cortical Function in Nondeprived Smokers Performing the Stroop Task.
Periodical: Neuropsychopharmacology Index Medicus:
Authors: Xu, Mendrek A, Cohen MS, Monterosso JR, Simon SL, Jarvik ME, Olmstead RE, Brody AL ART
Yr: 0 Vol: Nbr: Abs: Pg: