Project 4

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SUMMARY MDMA (‘ecstasy’) and ketamine are drugs of abuse that have steadily gained in popularity. Compared to more traditional stimulants or narcotics, however, less is known about their mode of action, their subjective effects, and how these effects promote continued use. Our objective is to develop a theoretically-informed characterization of the effects of MDMA, methamphetamine and ketamine on the neurobehavior of specific circuits for processing risk and reward, the connectivity of these circuits, and how these circuits and their connectivity predict acute drug experience and drug use outcomes. We will first pursue optogenetic techniques for neural control to map the effects of MDMA, methamphetamine and ketamine on neurobehavior related to risk and reward in rodents. Second, we will use neuroimaging to map both the acute and cumulative influence of these drugs on neurobehavioral targets in humans, focusing on risk and reward circuits and accompanying behaviors. We will also assess the extent to which these influences of drug exposure on neurobehavioral targets predict future use patterns over a follow up period of 6 months. Third, we will extend our approach to characterizing the acute and cumulative effects of MDMA, methamphetamine and ketamine on whole brain connectivity and associated behaviors such as degree of control. Under this third objective we will assess the prediction of future use patterns over the same follow up period. The results will advance our scientific understanding about why people are motivated to use these drugs, and provide a foundation for future investigations of tailored intervention strategies.