Neurobiology of Reward Choice

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Project Summary/Abstract Cocaine abuse has persisted as a major public health concern within the United States for several decades despite substantial efforts to develop therapeutic strategies for its treatment. In particular, medications development efforts have failed to yield a single FDA-approved or generally accepted pharmacotherapy for cocaine dependence. Prominent and problematic consequences of prolonged drug abuse include the persistent devaluation of natural nondrug rewards that previously functioned as effective reinforcers prior to drug exposure, and an increase in the “incentive salience” of drug-associated stimuli, leading to the model that drugs “hijack” the brain's natural reward system. The purpose of this proposal is to determine whether a behavioral modification strategy encompassing occasional, unexpected presentation of a high-value, alternate reinforcer will increase the hedonic value and/or motivational salience of a natural reward such that it will reduce cocaine seeking in rats. In Aim 1, we will use an operant cocaine vs. food choice procedure to determine whether a rare, unexpected reward will shift preferred responding from cocaine to food and alter associated dopamine transmission in the nucleus accumbens. Aim 2 will examine the consequences of this behavioral manipulation in a model of relapse-like behavior.