Protocol Number: 03-AA-0013

Title:

Brain Activation in Response to Motivational and Affective Stimuli: Pharmacological Manipulations

Number:

03-AA-0013

Summary:

This study seeks more information about the biology of substance dependency by exploring the brain areas involved in feeling positive and negative emotions. Specifically, it will determine whether a brain chemical called dopamine affects activity in certain brain regions during performance of a game that involves winning and losing money. Brain activity will be examined using magnetic resonance imaging (MRI), a test that uses a magnetic field and radio waves to produce images of brain structure and function.

Young to middle-aged healthy adults may participate in this study. Candidates will be screened with a medical history, physical examination, electrocardiogram (EKG), psychiatric interview, and blood and urine tests. Participants will be assigned to one of the two study procedures, as follows:

Tyrosine/Phenylalanine

This study requires two overnight stays at the NIH Clinical Center. For each stay, subjects are admitted to the hospital the afternoon before the MRI scan. From the time of admission until after the scan, their diets are restricted to food relatively low in amino acids, prepared by NIH dietitians. The next day, participants undergo MRI scanning. For this procedure, the subject lies on a table that is moved into the scanner, a metal cylindrical machine. Earplugs are worn to muffle loud noises that occur with electrical switching of the radio frequency circuits. Imaging of brain structure takes about 10 to 15 minutes. Additional scans are then taken to measure brain activity while the subject plays simple computer games for money. These scans take about another 20 to 45 minutes. Five hours before the MRI, the subject drinks one of two beverages containing amino acids. A different beverage is given for each of the two visits: one drink lacks the essential amino acids tyrosine and phenylalanine, from which the body makes dopamine; the other contains balanced amounts of these two amino acids. Finally, subjects fill out mood-rating questionnaires before and after drinking each of the beverages.

Dextroamphetamine

This study requires two outpatient visits to the NIH Clinical Center. For one visit, participants are given an injection of 0.2 mg/kg body weight of the drug dextroamphetamine; for the other, they are given an injection of saline (salt water). After each injection, they undergo MRI scanning while playing computer games for money, as described above. They will fill out mood-rating questionnaires before and after each brain scan.

Sponsoring Institute:

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION AND EXCLUSION CRITERIA:

Subjects are physically healthy as determined by medical evaluation at the NIAAA outpatient clinic. In particular, subjects must demonstrate no cardiovascular or blood pressure abnormalities, such as a resting blood pressure of 140/90 or greater.

Are between 18-65 years of age.

Have 20/20 vision or wear corrective contact lenses. Plastic glasses with pop-in lenses of different strengths are available in the NMR center for use with nearsighted subjects who do not wear contacts.

Have no ferromagnetic objects in their bodies which might be adversely affected by MRI (e.g. surgical clips; metal fragments in or near brain; eye or blood vessels; cardiac or neurological pacemaker; cochlear or eye implant - any doubt about absence of these objects will result in exclusion from this study).

Test HIV negative.

Have no indication of any organic brain syndrome.

Do not meet criteria for any present or past Axis I psychiatric disorder, including nicotine dependence. Smokers will be excluded.

Have no active homicidal or suicidal ideation, or active symptoms of post-traumatic stress disorder.

Are not currently receiving psychotropic medication or medication likely to affect brain neurotransmitter systems.

Have no indication of recent drug use as evidence by urine drug screen and self-report.

Are not pregnant or lactating.

Special Instructions: Currently Not Provided

Keywords:

Limbic System

Amphetamine

Dopamine

Brain Imaging

Cerebral Blood Flow

Cerebral Blood Volume

Alcoholism

Tyrosine Depletion

Amino Acids

Affect

Recruitment Keywords:

Healthy Volunteer

HV

Conditions:

Drug Dependence

Investigational Drug(s):

D-amphetamine

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Holland P, Mushinski M. Costs of alcohol and drug abuse in the United States, 1992. Alcohol/Drugs COI Study Team.

Stat Bull Metrop Insur Co. 1999 Oct-Dec;80(4):2-9.

Koob GF. Neurobiology of addiction. Toward the development of new therapies. Ann N Y Acad Sci. 2000;909:170-85. Review.

Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Hitzemann R, Chen AD, Dewey SL, Pappas N. Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent

subjects. Nature. 1997 Apr 24;386(6627):830-3.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

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