Prior Cocaine Experience Impairs Normal Phasic Dopamine Signals of Reward Value in Accumbens Shell

摘要

Dopamine signals have repeatedly been linked to associative learning and motivational processes. However, there is considerably less agreement on a role for dopamine in reward processing, and therefore whether neuroplastic changes in dopamine function following chronic exposure to drugs of abuse such as cocaine may impair appropriate valuation of rewarding stimuli. To quantify this, we voltammetrically measured real-time dopamine release in the nucleus accumbens (NAc) core or shell while rats received unsignaled deliveries of either a small (1 pellet) or large (2 pellets) reward. In drug-naive controls, core dopamine signals did not discriminate between reward size at any point, while in the shell dopamine encoded magnitude differences only in a slower postpeak period. Despite this lack of discrimination between rewards by the peak DA response, controls easily discriminated between reward options in a subsequent choice task. In contrast, phasic dopamine reward signals were strongly altered by cocaine experience; core dopamine decreased peak response but increased discrimination between reward magnitudes while shell lost phasic responses to reward receipt altogether. Notably, animals with cocaine-associated alterations in dopamine signals for reward magnitude failed to subsequently discriminate between reward options. These findings suggest that cocaine self-administration alters the ability for dopamine signals to appropriately assign value to rewards and thus may in part contribute to later deficits in behaviors that depend on appropriate outcome valuation.