Individual Variation in Dopamine Encoding of Incentive Salience

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DESCRIPTION (provided by applicant): Addictive foods and drugs are never administered in isolation from salient discrete and contextual stimuli. The formation of associative memories allows for the linking of these stimuli to unconditioned rewarding effects, such that these cues obtain the ability to predict future reinforcement. These conditioned stimuli (CS) often become desired themselves and individuals vary in the degree to which this occurs. Recent evidence suggests the magnitude by which a CS is attractive and attributed with motivational meaning may be a function of dopamine (DA) signaling in the brain. We have been studying this in the rat using a conditioning task known as autoshaping. In this task an extendable/retractable lever is the CS that predicts reward. With repeated trials rats develop a conditioned response (CR); the specific CR performed varies across a population. For example, some rats approach and interact with the lever CS instead of approaching the location of food delivery ("sign-trackers"), while other rats do the opposite ("goal-trackers"). Antagonizing DA receptors in a region of the ventral striatum known as the nucleus accumbens core (NAcC) reduces this lever-directed behavior, while leaving goal-directed pellet retrieval intact. Therefore, DA signaling in the NAcC is hypothesized to selectively encode the attribution of incentive salience to the lever CS. The proposed research investigates individual variability in DA signaling underlying motivation- and reward-learning using the electrochemical technique Fast Scan Cyclic Voltammetry (FSCV). This technique allows for detecting real-time alterations in DA concentration in the awake-behaving rat. In two aims, the studies will ask (1) whether individual variability in the propensit to attribute motivational meaning to discrete reward-paired cues, such as the lever, is differentially encoded by DA signaling in the ventral and dorsal striatum; and (2) how variability in behavioral performance and DA signaling investigated in Aim 1 are modulated by environmental contexts that are predictive of reward availability or lack-there-of, therefore "setting the occasion" for pursuit of reward in the autoshaping task. By understanding variability in how reward-predictive stimuli motivate us to seek reinforcement we can better treat addictive disorders with novel cognitive-behavioral and pharmacotherapeutic techniques that are tailored to specific individuals.