PHARMACOLOGICAL ANALYSIS OF THE SCRATCHING PRODUCED BY DOPAMINE D-2 AGONISTS IN SQUIRREL-MONKEYS

Several dopamine agonists, administered i.m., produced persistent, exc essive and non-localized scratching in squirrel monkeys (Saimiri sciur eus). Studies were conducted with a series of drugs to determine the p harmacological mechanisms responsible for this effect. All of the dopa mine D-2 agonists studied produced dose-related increases in scratchin g, whereas several dopamine D-1 receptor agonists, indirect dopamine a gonists and drugs acting on other receptors failed to produce dose-rel ated increases in scratching. The scratching produced by D-2 agonists was stereospecific; (-)-NPA produced scratching whereas its (+)-enanti omer was inactive up to doses 300-fold higher. Scratching induced by q uinpirole was attenuated by both D-2 and D-1 antagonists, and this ant agonism was stereospecific, with the D-2 antagonist (-)-eticlopride, b ut not its enantiomer, active. Sensitivity developed to the effects of D-2 agonists with the quinpirole dose-effect curve shifting to the le ft by a factor of approximately 64. Two partial D-2 receptor agonists (SDZ 208-911 and SDZ 208-912) had limited efficacy in producing scratc hing, however, one partial D-2 receptor agonist (terguride) was fully efficacious, suggesting that there are spare receptors for this effect . The peripherally active dopamine antagonist domperidone and the hist amine antagonist diphenhydramine also reduced the scratching induced b y D-2 agonists, but not to the same extent as centrally acting D-2 ant agonists. Scratching in squirrel monkeys is an effect that appears to be due to agonist actions at D-2 receptors, and may be mediated by a r elease of histamine. This behavioral activity may be useful as an in v ivo indication of D-2 receptor activity in primates.