Rosenzweig-Lipson S, Hesterberg P, Bergman J
Harvard University, Department of Psychology, Cambridge, MA 01238.
Psychopharmacology (Berl). 1994 Sep;116(1):9-18. doi: 10.1007/BF02244865.
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, 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 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, and d-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.
采用连续观察程序，在松鼠猴中比较了选择性D1和D2、非选择性以及间接作用的多巴胺激动剂的行为效应。D1激动剂包括SKF 81297、SKF 82958和R(+)-6-溴-APB，它们使静止姿势和头部运动的频率呈剂量依赖性增加，对蜷缩或抓挠几乎没有影响。相比之下，被认为是D1部分激动剂的SKF 75670和R-SKF 38393，其作用与D1拮抗剂SCH 39166相当。也就是说，D1部分激动剂增加了蜷缩的持续时间，而没有显著改变静止姿势、头部运动或抓挠的频率。与D1激动剂不同，D2激动剂(+)-PHNO、喹吡罗和溴隐亭增加了抓挠的频率，但并未持续改变其他可观察到的行为。间接多巴胺激动剂可卡因、GBR 12909和d-苯丙胺以及非选择性D1/D2激动剂CY 208-243（但不包括(-)阿扑吗啡）的作用与D1激动剂如SKF 81297相当。也就是说，这些药物中的每一种都增加了静止姿势和头部运动的频率，对抓挠或蜷缩几乎没有影响。此外，D1激动剂SKF 82958和间接多巴胺激动剂可卡因的作用可被D1拮抗剂SCH 39166可逆性拮抗。目前的结果表明：1) 猴子中D1和D2激动剂的行为效应在性质上不同；2) 推测内在活性不同的D1激动剂具有不同的效应；3) 间接多巴胺激动剂的效应与推测具有高内在活性的D1激动剂相当。
