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A Brain Imaging Study Into Nicotine Induced Dopamine Release in Cigarette Smokers.

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ClinicalTrials.gov Identifier: NCT00396669
Recruitment Status : Unknown
Verified March 2012 by VEINSHTEIN AVIV, Hadassah Medical Organization.
Recruitment status was:  Recruiting
First Posted : November 7, 2006
Last Update Posted : March 27, 2012
Sponsor:
Information provided by (Responsible Party):
VEINSHTEIN AVIV, Hadassah Medical Organization

Brief Summary:
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 or disease Intervention/treatment Phase
Tobacco Use Disorder Drug: Bupropion Not Applicable

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: A Brain Imaging Study Into Nicotine Induced Dopamine Release in Cigarette Smokers, Using 11 C Raclopride in Positron Emission Tomography (PET)
Study Start Date : July 2007
Estimated Primary Completion Date : July 2012
Estimated Study Completion Date : July 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dopamine release Drug: Bupropion
We measure dopamine release at the striatum using 11 C Raclopride at baseline and after smoking a cigarette

Drug: Bupropion
Brain imaging after treatment with Bupropion
Other Name: Zyban




Primary Outcome Measures :
  1. Dopamine D2 receptor occupancy before and after smoking a cigarette with nicotine [ Time Frame: 30 minutes ]

Secondary Outcome Measures :
  1. Subjective measures of craving, anxiety and depression. [ Time Frame: 30 minutes ]


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Ages Eligible for Study:   21 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • smokers who smoked 15 cigarettes/day and who met the DSM-IV criteria for nicotine dependence

Exclusion Criteria:

  • Subjects who are diagnosed as suffering from psychotic illness according to DSM-IV (Axis 1)22, or with a history of CNS disease, a history of infection that might affect CNS (HIV, syphilis, cytomegalovirus, herpes), or a history of head injury with loss of consciousness will be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00396669


Contacts
Contact: Aviv M Weinstein, Ph.D 00 972 2 6776705 avivweinstein@yahoo.com

Locations
Israel
Hadassah Medical Organization Recruiting
Jerusalem, Israel, 91120
Contact: Hadas Lemberg, Ph.D    00 972 2 6777572    lhadas@hadassah.org.il   
Principal Investigator: Aviv M Weinstein, Ph.D         
Sponsors and Collaborators
Hadassah Medical Organization
Investigators
Principal Investigator: Aviv M Weinstein, Ph.D Hadassah Medical Organization
Principal Investigator: Moshe Bocher, M.D Hadassah Medical Organization

Responsible Party: VEINSHTEIN AVIV, Senior Research Fellow, Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT00396669     History of Changes
Other Study ID Numbers: 291006 HMO-CTIL
First Posted: November 7, 2006    Key Record Dates
Last Update Posted: March 27, 2012
Last Verified: March 2012

Keywords provided by VEINSHTEIN AVIV, Hadassah Medical Organization:
Nicotine
Dopamine
Imaging
Raclopride
Addiction
Genetics

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Nicotine
Dopamine
Bupropion
Raclopride
Dopamine Agents
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Cardiotonic Agents
Sympathomimetics
Protective Agents