Cue-Evoked Cocaine "Craving": Role of Dopamine in the Accumbens Core

Drug-associated cues can acquire powerful motivational control over the behavior of addicts, and can contribute to relapse via multiple, dissociable mechanisms. Most preclinical models of relapse focus on only one of these mechanisms: the ability of drug cues to reinforce drug-seeking actions following a period of extinction training. However, in addicts, drug cues typically do not follow seeking actions; they precede them. They often produce relapse by evoking a conditioned motivational state ("wanting" or "craving") that instigates and/or invigorates drug-seeking behavior. Here we used a conflict-based relapse model to ask whether individual variation in the propensity to attribute incentive salience to reward cues predicts variation in the ability of a cocaine cue to produce conditioned motivation (craving) for cocaine. Following self-administration training, responding was curtailed by requiring rats to cross an electrified floor to take cocaine. The subsequent response-independent presentation of a cocaine-associated cue was sufficient to reinstate drug-seeking behavior, despite the continued presence of the adverse consequence. Importantly, there were large individual differences in the motivational properties of the cocaine cue, which were predicted by variation in the propensity to attribute incentive salience to a food cue. Finally, a dopamine antagonist injected into the nucleus accumbens core attenuated, and amphetamine facilitated, cue-evoked cocaine seeking, implicating dopamine signaling in cocaine cue-evoked craving. These data provide a promising preclinical approach for studying sources of individual variation in susceptibility to relapse due to conditioned craving and implicate mesolimbic dopamine in this process.