Discriminative stimulus effects of dopaminergic agents in rhesus monkeys

Recent reports have shown that treatment with dopamine reuptake inhibitors can selectively decrease responding maintained by low doses of cocaine in rhesus monkeys. This may occur because response-independent delivery of a reuptake inhibitor and response-dependent cocaine have common effects. One behavioral effect that dopamine reuptake inhibitors and cocaine share is their ability to serve as a discriminative stimulus. To compare discriminative effects of several dopaminergic agents with their ability to attenuate cocaine-maintained responding, three rhesus monkeys were first trained to discriminate intravenous injections of cocaine (0.1 mg/kg) from saline. Following generalization testing with various doses of cocaine (0.001-1.0 mg/kg), the relative potencies of phentermine (0.03-1.0 mg/kg), d-amphetamine (0.01-1.0 mg/kg), GBR 12,909 (0.01-1.0 mg/kg), and buspirone (0.03-0.56 mg/kg) to substitute for cocaine were assessed. Each drug except buspirone resulted in predominantly cocaine-appropriate responding at doses that were generally without rate-decreasing effect. The ED50 for the ability of these drugs to substitute for cocaine exhibited the same rank order as that for their effectiveness in decreasing cocaine-maintained responding. Thus, the current results show that the potencies of dopaminergic drugs to decrease cocaine-maintained responding and substitute for cocaine in a drug discrimination paradigm are related.