Differential effects of dopamine D1 and D2 receptor agonists on schedule-controlled behavior of squirrel monkeys

The effects of dopamine agonists differing in affinity and selectivity at D1 and D2 types of dopamine receptors were compared in squirrel monkeys responding under two different schedules of reinforcement: a fixed-interval (FI) schedule of stimulus-shock termination and a fixed-ratio (FR) schedule of food presentation. Dopamine D1 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 D2 agonists included (+)-PHNO, quinpirole and N-0434; nonselective DA agonists included R(-)-apomorphine and CY 208-243. The behavioral effects of D1 agonists differed qualitatively from those of D2 and nonselective DA agonists. D1 agonists produced dose-related decreases in both FI and FR responding, with comparable doses being effective under the two schedules. The rank order of potency for the rate-decreasing effects of these drugs was R(+)-6-Br-APB > SKF 75670 > SKF 82958 > R-SKF 38393 > SKF 81297 > SKF 77434 > SKF 83189 > dihydrexidine > R, S-SKF 38393. In contrast, D2 and nonselective DA agonists produced significant increases in rates of FI responding at doses that reduced FR response rates. The rank order of potency for the rate-increasing effects of these drugs under the FI schedule was (+)-PHNO > N-0434 > R-apomorphine > CY 208-243 > quinpirole.(ABSTRACT TRUNCATED AT 250 WORDS)