COCAINE ADDICTION -- ALTERATIONS IN REWARD CIRCUITRY

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DESCRIPTION: (provided by applicant) This proposal, entitled "Cocaine addiction: Mapping alterations in reward circuitry," is a request for a NIDA R01 submitted in response to the RFA "Cognitive Approaches to Addictive Processes (RFA DA-01-001). To study reward circuitry in humans, the investigators have developed multiple drug infusion protocols and cognitive neuroscience studies for use with functional magnetic resonance imaging (fMRI). This R01 research proposal asks two fundamental questions: (1) Does a common circuitry process reward expectancy and reward outcome information across distinct categories of reward, and (2) How does this circuitry function differently in drug naive vs. cocaine dependent subjects for distinct categories of reward? To address these questions, this proposal outlines a strategy to evaluate the function of reward circuitry with regard to expectancy and reward outcome across three distinct categories of rewarding stimuli, namely pharmacological (morphine), monetary, and social reward. It further seeks to compare the function of this circuitry across matched cohorts of drug dependent subjects and healthy volunteers. The experiments proposed have already been successfully performed in separate cohorts of healthy controls, and piloted in cocaine dependent subjects. These studies demonstrate unique patterns of activation for the nucleus accumbens, amygdala, sublenticular extended amygdala of the basal forebrain, ventral tegmentum, and orbital gyrus with regard to reward expectancy and reward outcome. Specific Aim 1 is designed to evaluate the consistency of the fMRI response with regard to reward expectancy and reward outcome within the same individuals receiving three distinct categories of reward. These rewards include a pharmacological reward in the form of low-dose morphine infusions, non-drug reward in the form of money, and social reward in the form of beautiful vs. average faces. Specific Aims 2-4 apply each of these experiments to matched cohorts of cocaine dependent subjects and healthy controls to evaluate reward circuitry differences in the processing of expectancy information and outcome information between groups. Across these experiments, it is predicted that reward circuitry function will be diminished for non-drug reward in drug-dependent subjects relative to healthy volunteers, and that this alteration will be most pronounced for expectancy systems processing probability information about rewarding stimuli.