Enhanced responding for conditioned reward produced by intra-accumbens amphetamine is potentiated after cocaine sensitization

The mesolimbic dopamine (DA) system has been implicated in conditioned rewa rd (CR), locomotor sensitization, and the reinforcing properties of psychom otor stimulants. Stimuli with formerly motivationally neutral properties th at gain incentive properties by their predictive association with primary r einforcers are termed conditioned, or secondary, reinforcers. In these expe riments, we investigated whether cocaine sensitization could potentiate aug mented responding for CR produced by intra-accumbens amphetamine. After sub jects were trained on the CR paradigm for 14 days, they received a regimen of cocaine sensitization or saline injections. On 2 test days, 8-10 days la ter, subjects were given amphetamine (6 mu g/0.5 mu l) or saline infusions into the nucleus accumbens (NAc) and responding for CR was measured using t he "acquisition of a new response" paradigm. Responding on one novel lever resulted in the delivery of the conditioned stimulus (conditioned reinforce r, or CR lever), whereas responding on the other lever resulted in no CR st imulus presentation (NCR lever). Animals sensitized to cocaine showed incre ased responding on the CR lever after intra-NAc saline and potentiated CR l ever responding after intra-NAc amphetamine. No differences in responding b etween the cocaine- and saline-treated groups on the NCR lever after the ch allenge were found. Locomotor sensitization under these conditions was conf irmed in a separate group of subjects. These findings show that prior expos ures to cocaine results in changes that potentiate the ability of intra-NAc amphetamine to enhance CR. Repeated stimulant drug use may induce long-ter m neuronal adaptations that result in increased sensitivity to the behavior al, or incentive motivational, effects of stimulant drugs.