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.

Public Health Relevance

People differ in their initial behavioral responses to psychomotor stimulant drugs in ways that affect risk for future use or abuse. One source of individual differences may be variation in the brain circuits that mediate the drugs' effects, the same circuits that process other types of reward. In this study, we will examine individual differences in responses to a single dose of methamphetamine on the brain reward circuit in healthy adults, and determine the relationship of these effects to the behavioral rewarding effects of the drug.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
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Grant, Steven J
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University of Chicago
Schools of Medicine
United States
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