Pellón R, Flores P, Alling K, Witkin J M, Katz J L
Psychobiology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA.
J Pharmacol Exp Ther. 1995 Apr;273(1):138-45.
Several dopamine agonists, administered i.m., produced persistent, excessive and non-localized scratching in squirrel monkeys (Saimiri sciureus). Studies were conducted with a series of drugs to determine the pharmacological mechanisms responsible for this effect. All of the dopamine D2 agonists studied produced dose-related increases in scratching, whereas several dopamine D1 receptor agonists, indirect dopamine agonists and drugs acting on other receptors failed to produce dose-related increases in scratching. The scratching produced by D2 agonists was stereospecific; (-)-NPA produced scratching whereas its (+)-enantiomer was inactive up to doses 300-fold higher. Scratching induced by quinpirole was attenuated by both D2 and D1 antagonists, and this antagonism was stereospecific, with the D2 antagonist (-)-eticlopride, but not its enantiomer, active. Sensitivity developed to the effects of D2 agonists with the quinpirole dose-effect curve shifting to the left by a factor of approximately 64. Two partial D2 receptor agonists (SDZ 208-911 and SDZ 208-912) had limited efficacy in producing scratching, however, one partial D2 receptor agonist (terguride) was fully efficacious, suggesting that there are spare receptors for this effect. The peripherally active dopamine antagonist domperidone and the histamine antagonist diphenhydramine also reduced the scratching induced by D2 agonists, but not to the same extent as centrally acting D2 antagonists. Scratching in squirrel monkeys is an effect that appears to be due to agonist actions at D2 receptors, and may be mediated by a release of histamine. This behavioral activity may be useful as an in vivo indication of D2 receptor activity in primates.
几种肌肉注射的多巴胺激动剂在松鼠猴（Saimiri sciureus）身上引发了持续、过度且无局部定位的抓挠行为。我们使用一系列药物进行了研究，以确定造成这种效应的药理机制。所有研究的多巴胺D2激动剂均产生了与剂量相关的抓挠增加，而几种多巴胺D1受体激动剂、间接多巴胺激动剂以及作用于其他受体的药物均未产生与剂量相关的抓挠增加。D2激动剂引发的抓挠具有立体特异性；（-）-NPA会引发抓挠，而其（+）-对映体在高达300倍剂量时仍无活性。喹吡罗诱导的抓挠可被D2和D1拮抗剂减弱，且这种拮抗作用具有立体特异性，D2拮抗剂（-）-依托必利有活性，而其对映体无活性。对D2激动剂的敏感性增强，喹吡罗剂量效应曲线向左移动约64倍。两种部分D2受体激动剂（SDZ 208-911和SDZ 208-912）在引发抓挠方面效果有限，然而，一种部分D2受体激动剂（替告瑞林）效果完全，这表明存在这种效应的备用受体。外周活性多巴胺拮抗剂多潘立酮和组胺拮抗剂苯海拉明也能减少D2激动剂诱导的抓挠，但程度不如中枢作用的D2拮抗剂。松鼠猴的抓挠行为似乎是由于D2受体上的激动剂作用，可能由组胺释放介导。这种行为活动可能作为灵长类动物体内D2受体活性的一种指示。
