DIFFERENTIAL-EFFECTS OF DOPAMINE D-1 AND D-2 RECEPTOR AGONISTS ON SCHEDULE-CONTROLLED BEHAVIOR OF SQUIRREL-MONKEYS

The effects of dopamine agonists differing in affinity and selectivity at D-1 and D-2 types of dopamine receptors were compared in squirrel monkeys responding under two different schedules of reinforcement: a f ixed-interval (FI) schedule of stimulus-shock termination and a fixed- ratio (FR) schedule of food presentation. Dopamine D-1 family agonists included dihydrexidine, SKF 81297, SKF 82958, R-6-Br-APB, SKF 83189, SKF 77434, SKF 75670 and R- and R, S-SKF 38393. Dopamine D-2 agonists included (+)-PHNO, quinpirole and N-0434; nonselective DA agonists inc luded R(-)-apomorphine and CY 208-243. The behavioral effects of D-1 a gonists differed qualitatively from those of D-2 and nonselective DA a gonists. D-1 agonists produced dose-related decreases in both FI and F R responding, with comparable doses being effective under the two sche dules. The rank order of potency for the rate-decreasing effects of th ese drugs was R(+)-6-Br-APB > SKF 75670 > SKF 82958 > R-SKF 38393 > SK F 81297 > SKF 77434 > SKF 83189 > dihydrexidine > R, S-SKF 38393. In c ontrast, D-2 and nonselective DA agonists produced significant increas es in rates of FI responding at doses that reduced FR response rates. The rank order of potency for the rate-increasing effects of these dru gs under the FI schedule was (+)-PHNO > N-0434 > R-apomorphine > CY 20 8-243 > quinpirole. Based on the correspondence between the potencies of DA agonists in these experiments and their reported potencies for b inding to D-1 and D-2 receptors, the contrasting effects of D-1 agonis ts, on the one hand, and of D-2 and nonselective agonists, on the othe r, likely are mediated predominantly by their actions at, respectively , D-1 and D-2 receptors.