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

March 26, 2012 updated by: VEINSHTEIN AVIV, Hadassah Medical Organization

A Brain Imaging Study Into Nicotine Induced Dopamine Release in Cigarette Smokers, Using 11 C Raclopride in Positron Emission Tomography (PET)

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Enrollment (Anticipated)

24

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Jerusalem, Israel, 91120
        • Recruiting
        • Hadassah Medical Organization
        • Principal Investigator:
          • Aviv M Weinstein, Ph.D
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Zyban

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Dopamine D2 receptor occupancy before and after smoking a cigarette with nicotine
Time Frame: 30 minutes
30 minutes

Secondary Outcome Measures

Outcome Measure
Time Frame
Subjective measures of craving, anxiety and depression.
Time Frame: 30 minutes
30 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hadassah Medical Organization

Investigators

  • Principal Investigator: Aviv M Weinstein, Ph.D, Hadassah Medical Organization
  • Principal Investigator: Moshe Bocher, M.D, Hadassah Medical Organization

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Anticipated)

July 1, 2012

Study Completion (Anticipated)

July 1, 2012

Study Registration Dates

First Submitted

November 6, 2006

First Submitted That Met QC Criteria

November 6, 2006

First Posted (Estimate)

November 7, 2006

Study Record Updates

Last Update Posted (Estimate)

March 27, 2012

Last Update Submitted That Met QC Criteria

March 26, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 291006 HMO-CTIL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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