DOPAMINE AND RISKS FOR DRUG ABUSE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. PURPOSE The purpose of this study is to evaluate whether alterations in dopamine (DA) neurotransmission predate and may influence risks for drug abuse in humans. Derangements in dopamine function have been observed in several populations of drug abusers in recent neuroimaging research. However, it remains unclear whether these alterations are a cause or a consequence of chronic drug use. Two psychosocial factors that have been strongly associated with the development and course of substance use disorders are risk-taking behavior and environmental stress. In this study, we will use positron emission tomography (PET) technology to examine whether dopaminergic responses to amphetamine are associated with individual differences in either of these variables in healthy young adults. We suggest that dampened DA sensitivity to drugs is a risk factor for substance abuse and that risk taking and stress increase risks for drug abuse through this mechanism. DESIGN Subjects will be healthy young adults, ages 18 through 29, recruited by advertisements and posted flyers from the Baltimore metropolitan area. Respondents who appear to qualify for the study based on an initial telephone screen will be invited to our offices to provide informed consent. The research will be conducted in two phases. Phase 1: In-person screening will include a psychiatric diagnostic interview and completion of several self-report forms. A brief medical history will also be obtained. Individuals who qualify will complete a laboratory performance session that includes administration of five computer-based measures of trait impulsivity. Phase 2: Subjects who complete the laboratory performance session will be asked to provide informed consent for a positron emission tomography (PET) study. Additional screening needed to assess subjects' eligibility to participate in the PET scans will include a history and physical exam, standard laboratory tests (i.e., blood chemistry panel, CBC, PT, PTT, TSH and urinalysis) and electrocardiogram (EKG). Qualified participants will participate in two [11C]raclopride PET scans measuring amphetamine-induced DA release. A magnetic resonance imaging (MRI) scan will be conducted prior to the PET scans for coregistration of emission images. TIMELINE: Telephone screen Phase 1 in-person screening and assessment Laboratory performance session Phase 2 screening MRI scan [11C]raclopride PET scans Recruitment, screening, psychological assessments, and behavioral performance sessions will be conducted in the research offices of the Principal Investigator at the University of Maryland School of Nursing. History and physical exams, screening EKGs and standard laboratory tests will be done at the University of Maryland School of Medicine General Clinical Research Center (UM-GCRC). MRIs and PET scans will be conducted at the Johns Hopkins Hospital Department of Radiology.