BEHAVIORAL-EFFECTS OF DOPAMINERGIC AGONISTS AND ANTAGONISTS ALONE AND IN COMBINATION IN THE SQUIRREL-MONKEY

The effects on schedule-controlled operant behavior of the D-2 receptor agonist, quinpirole, and the D-1 agonist, SKF 38393, were assessed alone and in combination with selective dopamine-receptor antagonists. Squirrel monkeys (Saimiri sciureus) were trained to press a response key under fixed-interval and fixed-ratio schedules of food reinforcement. The fixed-interval schedule maintained relatively low rates of responding that increased up to food presentation. The fixed-ratio schedule maintained relatively constant high rates of responding. Quinpirole increased rates and disrupted the temporal pattern of responding under the fixed-interval schedule at doses (0.1-1.0 mg/kg) that decreased rates of responding under the fixed-ratio schedule. Under the fixed-interval schedule, the D-2 antagonists, spiperone (0.003-0.006 mg/ kg) and haloperidol (0.003-0.01 mg/kg), and the D-1 antagonist, SCH 23390 (0.03 mg/kg), shifted the quinpirole dose-effect curve to the right. The maximal effects of quinpirole were decreased at the highest doses of the antagonists. However, only spiperone antagonized effects of quinpirole on the rates of responding under the fixed-ratio schedule. The D-1 agonist, SKF 38393, dose-dependently (1.0-lO.0 mg/kg) decreased rates of responding under both schedules. Those effects were not antagonized by any doses studied of either spiperone (0.003 mg/kg) or SCH 23390 (0.003-0.3 mg/kg). Rather, both antagonists enhanced the effects of SKF 38393. The present study suggests significant differences between the effects of D-1 and D-2 agonists on schedule-controlled behavior, and differences in the antagonist actions of the D-2 antagonists haloperidol and spiperone. Further, the ''selective'' dopamine D-1 agonist, SKF 38393, has behavioral effects that cannot be antagonized by either a D-1 or D-2 antagonist, suggesting that some other mechanism has a significant role in mediating its behavioral effects.