Evidence for dopaminergic involvement in tolerance to the discriminative stimulus properties of cocaine.

Rats were trained to discriminate cocaine, 10.0 mg/kg, in a two-lever operant procedure. Dose-effect data for generalization to cocaine and substitution of apomorphine for the cocaine stimulus were determined. Subsequently, training was halted and either apomorphine, 2.5 mg/kg per 8 h, or cocaine, 20 mg/kg per 8 h, was administered for 7-9 days. During chronic administration, the efficacy of cocaine and apomorphine as discriminative stimuli was decreased. These data suggest that dopaminergic mechanisms may mediate tolerance to the discriminative stimulus properties of cocaine.