Wenger G.R., Hudzik T., Moore E., Wright D.W.
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Behav Pharmacol. 1996 Aug;7(4):384-394. doi: 10.1097/00008877-199608000-00010.
The ability of picrotoxin to antagonize selectively the effects of pentobarbital was investigated in pigeons and squirrel monkeys responding under a titrating matching-to-sample schedule of reinforcement. Under the titrating matching-to-sample baseline, the length of the delay changed as a function of the animal's matching accuracy. Picrotoxin (0.03-1mg/kg) failed to alter significantly the matching accuracy of pigeons; however, rate of responding was markedly suppressed at a dose of 1mg/kg. In squirrel monkeys responding under a similar schedule, picrotoxin (0.001-0.3mg/kg) was without significant effect. Selected doses of picrotoxin in both pigeons (0.3 and 0.56mg/kg) and squirrel monkeys (0.1 and 0.3mg/kg) failed to shift the pentobarbital or diazepam dose-response curve for mean delay length to the right. However, in both species, picrotoxin shifted the dose-response curve for pentobarbital on rate of responding to the right. No such shift was observed for the effect of diazepam on rate of responding. In both species, the combination of picrotoxin and phencyclidine shifted the dose-response curves for phencyclidine on rate of responding, but not mean delay, downward and to the left, in an apparent additive manner. Thus, picrotoxin failed to produce a significant pharmacological antagonism of the effects of pentobarbital, diazepam or phencyclidine on matching accuracy. This failure to observe an antagonism of the effects of pentobarbital on matching accuracy, at doses of picrotoxin that antagonized the effects of pentobarbital on rate of responding, suggests that the effects of pentobarbital on matching accuracy and rate of responding are mediated by different receptor sites.
在鸽子和松鼠猴按照滴定匹配样本强化程序做出反应的情况下,研究了印防己毒素选择性拮抗戊巴比妥作用的能力。在滴定匹配样本基线条件下,延迟时间的长短随动物匹配准确性的变化而变化。印防己毒素(0.03 - 1毫克/千克)未能显著改变鸽子的匹配准确性;然而,在1毫克/千克的剂量下,反应速率明显受到抑制。在类似程序下做出反应的松鼠猴中,印防己毒素(0.001 - 0.3毫克/千克)没有显著影响。在鸽子(0.3和0.56毫克/千克)和松鼠猴(0.1和0.3毫克/千克)中选定的印防己毒素剂量未能使戊巴比妥或地西泮对平均延迟时间的剂量反应曲线向右移动。然而,在这两个物种中,印防己毒素使戊巴比妥对反应速率的剂量反应曲线向右移动。地西泮对反应速率的影响未观察到这种移动。在这两个物种中,印防己毒素和苯环己哌啶的组合使苯环己哌啶对反应速率的剂量反应曲线以明显的相加方式向下和向左移动,但对平均延迟时间没有影响。因此,印防己毒素未能对戊巴比妥、地西泮或苯环己哌啶对匹配准确性的作用产生显著的药理学拮抗作用。在能拮抗戊巴比妥对反应速率作用的印防己毒素剂量下,未能观察到对戊巴比妥对匹配准确性作用的拮抗,这表明戊巴比妥对匹配准确性和反应速率的作用是由不同的受体位点介导的。