, Volume 116, Issue 1, pp 9-18

Observational studies of dopamine D1 and D2 agonists in squirrel monkeys

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Abstract

The behavioral effects of selective D1 and D2, nonselective, and indirectly acting dopamine agonists were compared in squirrel monkeys using continuous observation procedures. D1 agonists including SKF 81297, SKF 82958, andR(+)-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 andR-SKF 38393, which are considered to be D1 partial agonists, had effects comparable to those of the D1 antagonist SCH 39166. That is, the D1 partial agonists increased the duration of huddling without greatly altering the frequencies of stationary postures, head movements, or scratching. Unlike the D1 agonists, the D2 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, andd-amphetamine and the nonselective D1/D2 agonist CY 208–243, but not (−)apomorphine, had effects comparable to those of D1 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 D1 agonist SKF 82958 and the indirect dopamine agonist cocaine were surmountably antagonized by the D1 antagonist SCH 39166. The present results show that: 1) behavioral effects of D1 and D2 agonists in monkeys are qualitatively different; 2) D1 agonists presumed to differ in intrinsic activity have dissimilar effects; and 3) effects of indirect dopamine agonists are comparable to those of D1 agonists with presumably high intrinsic activity.

Animals used in this study were maintained in accordance with the guidelines of the Committee on Animals of the Harvard Medical School and the “Guide for Care and Use of Laboratory Animals” of the Institute of Laboratory Animal Resources, National Research Council, Department of Health, Education, and Welfare, Publication No. (NIH)85-23, revised 1985. This research was supported by USPHS grants DA03774, DA00499, MH07658. Facilities and services were provided by the New England Regional Primate Research Center (USPHS Division of Research Resources Grant RR000168). Portions of this work were presented at the Society for Neuroscience Meeting 18: A641.1 1992. This work was completed in partial fulfilment of the requirements for the doctor of philosophy degree for S.R.-L.