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

NCT ID: NCT00396669

Last Updated: 2012-03-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2012-07-31

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.

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.

Conditions

Tobacco Use Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Dopamine release

Group Type: EXPERIMENTAL

Bupropion

Intervention Type: DRUG

We measure dopamine release at the striatum using 11 C Raclopride at baseline and after smoking a cigarette

Bupropion

Intervention Type: DRUG

Brain imaging after treatment with Bupropion

Interventions

Bupropion

We measure dopamine release at the striatum using 11 C Raclopride at baseline and after smoking a cigarette

Intervention Type: DRUG

Bupropion

Brain imaging after treatment with Bupropion

Intervention Type: DRUG

Other Intervention Names

Zyban

Eligibility 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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Hadassah Medical Organization

OTHER

Sponsor Role: lead

Responsible Party

VEINSHTEIN AVIV

Senior Research Fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Aviv M Weinstein, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Hadassah Medical Organization

Moshe Bocher, M.D

Role: PRINCIPAL_INVESTIGATOR

Hadassah Medical Organization

Locations

Hadassah Medical Organization

Jerusalem, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

Aviv M Weinstein, Ph.D

Role: CONTACT

avivweinstein@yahoo.com

00 972 2 6776705

Facility Contacts

Hadas Lemberg, Ph.D

Role: primary

lhadas@hadassah.org.il

00 972 2 6777572

Other Identifiers

291006 HMO-CTIL

Identifier Type: -

Identifier Source: org_study_id