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.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005795:Generalization, Stimulus / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats
D003042:Cocaine; D001058:Apomorphine; D004298:Dopamine