Buspirone blocks the discriminative stimulus effects of apomorphine in monkeys

Three rhesus monkeys were trained to discriminate apomorphine (APO) from saline in a two-lever, food-reinforced drug discrimination procedure. After acquisition of the discrimination, the monkeys were given various doses of APO in combination with saline or buspirone before test sessions in which responses occurring on either lever were reinforced. Combinations of APO (0.01-0.08 mg/kg, IV) and saline resulted in a dose-related increase from 0 to 100% in the percentage of responses that occurred on the APO-appropriate lever. When buspirone (0.04-0.16 mg/kg, IV) was combined with APO, reductions from 100% to 0% APO-appropriate responding were seen following at least one dose combination in all three monkeys. A parallel shift to the right of the APO dose-response curve with buspirone was evident in 2 monkeys, indicating surmountable antagonism. In one case, a further increase in buspirone dose resulted in an insurmountable antagonism, i.e., increasing APO dose still resulted in primarily saline-appropriate responding. These results suggest that buspirone can function as a D2 dopamine (DA) receptor antagonist at behaviorally relevant doses.