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Determinants of Drug Preference in Humans

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Abstract Drug abuse remains an urgent public health problem. One way to reduce the burden of the problem is to identify risk factors for who will develop drug use problems. The fact that only a few of the many people who experiment with drugs progress to develop problem use suggests that individuals differ in vulnerability. One source of variability is initial response to a drug, at both the behavioral and neural levels. Individuals vary in their initial responses to drugs in ways that predict risk, and these individual differences in drug responses originate, in part, in individual responses in brain function. In this project, we will study individual differences in responses the prototypic stimulant, methamphetamine, by examining both its behavioral rewarding effects and its actions on the brain. Individuals differ in subjective responses to methamphetamine, and preliminary evidence indicates that these differences are related to reactivity of the reward circuit to monetary reward. In this project, we will use fMRI to examine the responses of the striatal-frontal reward circuit to methamphetamine, and determine how individual differences in the neural effects predict behavioral indices of drug liking and reward. First we will obtain indices of neural activity with fMRI after methamphetamine vs placebo: regional activation elicited by a reward task, task-related functional connectivity, and resting state functional connectivity. Then on separate sessions we will obtain indices of the behaviorally rewarding effects of methamphetamine: drug liking, drug (and dose) choice and attentional bias to a drug-paired stimulus. Understanding the relation between the neural response and behavioral response to the drug will extend our understanding of why people differ in positive responses to a stimulant drug.
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