OBSERVATIONAL STUDIES OF DOPAMINE D-1 AND D-2 AGONISTS IN SQUIRREL-MONKEYS

The behavioral effects of selective D-1 and D-2, nonselective, and indirectly acting dopamine agonists were compared in squirrel monkeys using continuous observation procedures. D-1 agonists including SKF 81297, SKF 82958, and R(+)-6-Br-APB produced dose-dependent increases in the frequencies of stationary postures and head movements and had little or no effect on either huddling or scratching. In contrast, SKF 75670 and R-SKF 38393, which are considered to be D-1 partial agonists, had effects comparable to those of the D-1 antagonist SCH 39166. That is, the D-1 partial agonists increased the duration of huddling without greatly altering the frequencies of stationary postures, head movements, or scratching. Unlike the D-1 agonists, the D-2 agonists (+)-PHNO, quinpirole, and bromocriptine increased the frequency of scratching, but did not consistently alter other observable behaviors. The indirect dopamine agonists cocaine, GBR 12909, and d-amphetamine and the nonselective D-1/D-2 agonist CY 208-243, but not (-)apomorphine, had effects comparable to those of D-1 agonists such as SKF 81297. That is, each of these drugs increased the frequencies of stationary postures and head movements with little or no effect on scratching or huddling. Additionally, effects of the D-1 agonist SKF 82958 and the indirect dopamine agonist cocaine were surmountably antagonized by the D-1 antagonist SCH 39166. The present results show that: 1) behavioral effects of D-1 and D-2 agonists in monkeys are qualitatively different; 2) D-1 agonists presumed to differ in intrinsic activity have dissimilar effects; and 3) effects of indirect dopamine agonists are comparable to those of D-1 agonists with presumably high intrinsic activity.