In the past decade, neuroimaging technology has expanded knowledge about the effects of drugs of abuse on brain neurocircuitry and has provided tools for increasing our understanding of the role that these circuits play in motivational behaviors and substance use disorders. Nevertheless, a persistent gap in our knowledge stems from the difficulties involved in trying to determine whether alterations in brain neurochemistry represent vulnerability factors or consequences of addiction in drug addicts. A challenging question that continues to plague this field is why some individuals are biologically more vulnerable to addiction than others. Two factors that have been strongly associated with the development and course of substance use disorders in clinical studies are impulsivity and environmental stress. There is growing evidence from preclinical studies that each of these factors may be associated with alterations in dopamine (DA) neurotransmission. These findings, coupled with clear evidence of DA involvement in drug abuse, suggest that relationships among impulsivity, chronic stress, and drug abuse may be mediated by the DA system. Nevertheless, the nature of these relationships is still poorly understood and human studies are lacking. In the proposed study, we will use PET technology to evaluate whether specific alterations in DA function predate drug abuse in humans and may increase risks for the development of drug use disorders. Specifically, we will examine whether striatal DA responses to amphetamine are associated with risk taking behavior or chronic stress in healthy, young adults with no history of substance abuse or dependence. Participants will complete a laboratory performance assessment of risk taking behavior and two [11C]raclopride PET scans measuring individual differences in amphetamine-induced DA release. Measures of life events stress will also be obtained. Secondary aims include exploratory analysis of associations with other lower-order dimensions of impulsivity and with early life stress. We hypothesize that dampened DA activity is a risk factor for the development of substance use disorders and that risk taking and chronic stress increase risks for drug abuse through this mechanism. Project Narrative By increasing our understanding of discrete neural processes that mediate vulnerability substance use disorders, the findings will contribute to the ongoing development of new and promising prevention and treatment strategies that take into account fundamental differences in genetic and environmental vulnerability factors across individuals.
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