Psychology of Reward and Punishment: Functional and Molecular Brain Imaging and Monoaminergic Correlates
- Brain imaging studies, genetic research, and investigations of stress have provided more information about the role of dopamine in processing reward and punishment, and in vulnerability to substance dependence. Researchers are interested in learning more about how the brain responds to rewards, including drugs of abuse, and how these responses may involve genetic factors or previous stressful events.
- Researchers intend to use the drug amphetamine to increase levels of dopamine in the brain and study the effects through two kinds of scanning: functional magnetic resonance imaging (fMRI) and positron emission tomography (PET).
- To examine the relationship among dopamine function, brain activity, reward processing, genetic profile and exposure to stress in normal healthy adults.
- To examine the variation in these factors between normal healthy adults and individuals with current cocaine-dependence.
- Individuals 18 to 45 years of age who are either current cocaine users or healthy volunteers with no history of substance abuse or dependence.
- The study will consist of an initial evaluation session and six study visits, four of which will involve fMRI scans (3 hours each) and two of which will involve PET scans (8 to 9 hours each).
- Cocaine-using participants will enter the inpatient clinical research ward at the National Institute on Drug Abuse Addiction Research Center the night before each scanning session and will be discharged the following day. Healthy volunteer subjects will not be required to stay overnight and will arrive as outpatients for the PET session. Participants will not be released until researchers have determined that participants are not experiencing significant effects of the drug.
- Initial session (1): Participants will complete questionnaires about past reactions to stressful situations, and will be trained to do thinking tasks that will be performed in fMRI visits. The tasks will be practiced in a mockup of an MRI machine.
- MRI sessions (2-5): Participants will receive either oral amphetamine or a placebo, and will perform thinking, short-term memory, and reward tasks during MRI scanning as directed by researchers.
- PET sessions (6-8): Participants will receive either oral amphetamine or a placebo, and will provide blood samples during the PET scanning sessions. Participants will have short breaks during the PET scanning sessions.
|Official Title:||Psychology of Reward and Punishment: Functional and Molecular Brain Imaging and Monoaminergic Correlates|
|Study Start Date:||December 2007|
|Estimated Study Completion Date:||December 2010|
Objective: This protocol will integrate functional brain imaging of reward processing, together with assessment of the response to oral dextroamphetamine (d-AMPH), monoaminergic genotyping, and evaluation of past exposure to stress, in order to examine: (1) the relationship between these factors (i.e. dopamine function, brain activity, reward processing, genetic profile and exposure to stress) in normal healthy adults; and (2) variation in these factors between normal healthy adults and individuals with current cocaine-dependence, and how this variation contributes to observed behavioral and functional differences between these populations.
Study Population: The study populations will consist of adult (18-45 years old) healthy volunteers with no history of substance abuse or dependence and a matched group of individuals with current primary cocaine-dependence.
Experimental Design and Method: After being medically cleared and giving informed consent, each participant will undergo fMRI (four sessions, on separate days) and PET scanning (two sessions, on separate days). All brain imaging sessions will take place after single-blind administration of either d-AMPH (0.43 mg/kg orally) or placebo. Functional MRI will commence after dosing and will include several measures (both cognitive and affective) designed to activate neural circuitry involved in the processing of reward and punishment. PET scanning will also take place after d-AMPH or placebo and will involve administration of the radioligand [18F] Fallypride to assess CNS dopamine function.
Outcome Measures: This study is concerned with differences in the noted factors between experimental cohorts (controls vs. cocaine-dependent adults) and conditions (baseline vs. post d-AMPH). The primary outcome measures, used to ascertain these differences, will be: (1) the percentage change in fMRI BOLD signal during performance of measures of reward processing and cognitive function; (2) alterations or differences in the binding potential of [18F]Fallypride; (3) variations in genes related to DArgic function between individuals and groups, and the contribution of this variation to other outcome measures; and (4) history of exposure to stressful events and its role in behavioral and functional outcomes.
|United States, Maryland|
|National Institute on Drug Abuse, Biomedical Research Center (BRC)|
|Baltimore, Maryland, United States, 21224|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|