Pentobarbital, diazepam and phencyclidine disrupt delayed matching performance: interactions with picrotoxin in...

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.