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Sponsored by: |
Hadassah Medical Organization |
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Information provided by: | Hadassah Medical Organization |
ClinicalTrials.gov Identifier: | NCT00396669 |
Dopamine (DA) plays a critical role in nicotine (and other) addiction and this drug is known to release DA in brain areas mediating reward and motivational processes. Although imaging studies show that release of DA follows smoking, little is known regarding how common genetic polymorphisms for three genes associated in some studies with smoking (dopamine D2 receptor, dopamine and serotonin transporter) interact with smoking status and modulate individual differences in nicotine-induced DA release and dopamine receptor occupancy, in vivo. The current proposal combines brain imaging and genomics ('imaging genomics') towards partially unraveling the complex relationship between smoking phenotype and common polymorphisms. Understanding whether genetic factors contribute to inter-individual variability in smoking is crucial for interpreting imaging results in the context of disease pathology. We hypothesize that a model of vulnerability to addiction based on interactions between genotype, receptor and transporter availability and in vivo nicotine-induced DA release will elucidate some of the fundamental neurochemical and neurogenetic circuits underlying addiction.
Condition | Intervention |
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Tobacco Use Disorder |
Procedure: PET Brain Imaging |
Study Type: | Interventional |
Study Design: | Diagnostic, Non-Randomized, Open Label, Uncontrolled, Factorial Assignment, Pharmacodynamics Study |
Official Title: | A Brain Imaging Study Into Nicotine Induced Dopamine Release in Cigarette Smokers, Using 11 C Raclopride in Positron Emission Tomography (PET) |
Estimated Enrollment: | 24 |
Study Start Date: | July 2007 |
Estimated Study Completion Date: | December 2009 |
Estimated Primary Completion Date: | April 2009 (Final data collection date for primary outcome measure) |
Dopamine plays a critical role in nicotine(and other) addiction and this drug is known to release DA in brain areas mediating reward and motivational processes. Although imaging studies show that release of DA follows smoking, little is known regarding how common some genetic polymorphisms proposed to play a role in nicotine dependence (e.g. DRD2, DAT and the serotonin transporter or SERT) interact with smoking status (non-smoker, ex-smoker, light smoker, present smoker) and modulate individual differences in nicotine-induced DA release and dopamine receptor occupancy, in vivo. Individual differences in dopaminergic tone could result in an under-stimulation of reward circuits which could put subjects at greater risk for seeking drug stimulation (that releases DA) as a means to compensate for this deficit and to temporarily activate these reward circuits. The current proposal combines brain imaging and genomics towards unraveling the complex relationship between smoking phenotype and common polymorphisms. Understanding whether genetic factors contribute to inter-individual variability is crucial for interpreting imaging results in the context of disease pathology.
Nicotine dependence is a complex process including initiation of smoking, persistence and difficulty in quitting. By comparing receptor occupancy, nicotine-induced DA release, and common genetic polymorphisms across smoking behaviors we will better understand the complex interactions between genetic makeup, personality and the several stages of nicotine addiction.
Ages Eligible for Study: | 21 Years to 50 Years |
Genders Eligible for Study: | Male |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Contact: Aviv M Weinstein, Ph.D | 00 972 2 6776705 | vaviv@hadassah.org.il |
Israel | |
Hadassah Medical Organization | Recruiting |
Jerusalem, Israel, 91120 | |
Contact: Arik Tzukert, DMD 00 972 2 6776095 arik@hadassah.org.il | |
Contact: Hadas Lemberg, Ph.D 00 972 2 6777572 lhadas@hadassah.org.il | |
Principal Investigator: Aviv M Weinstein, Ph.D |
Principal Investigator: | Aviv M Weinstein, Ph.D | Hadassah Medical Organization |
Principal Investigator: | Moshe Bocher, M.D | Hadassah Medical Organization |
Responsible Party: | Hadassah Medical Organization ( Dr Arik Zukert ) |
Study ID Numbers: | 291006 HMO-CTIL |
Study First Received: | November 6, 2006 |
Last Updated: | May 6, 2008 |
ClinicalTrials.gov Identifier: | NCT00396669 |
Health Authority: | Israel: Israeli Health Ministry Pharmaceutical Administration |
Nicotine Dopamine Imaging |
Raclopride Addiction Genetics |
Nicotine polacrilex Behavior, Addictive Dopamine Nicotine Mental Disorders |
Tobacco Use Disorder Raclopride Substance-Related Disorders Disorders of Environmental Origin |
Neurotransmitter Agents Tranquilizing Agents Cholinergic Agonists Molecular Mechanisms of Pharmacological Action Cardiotonic Agents Sympathomimetics Nicotinic Agonists Physiological Effects of Drugs Psychotropic Drugs Central Nervous System Depressants Dopamine Antagonists |
Cardiovascular Agents Antipsychotic Agents Cholinergic Agents Protective Agents Pharmacologic Actions Autonomic Agents Therapeutic Uses Ganglionic Stimulants Dopamine Agents Peripheral Nervous System Agents Central Nervous System Agents |