Conditioned Suppression and the Effects of Pentobarbital with Picrotoxin, Flumazenil, and R05-3663

Abstract

In two experiments, rats trained to lever press for food were maintained under a conditioned suppression procedure and then given an acute regime of drug administration involving pentobarbital (10 mg/kg). In both experiments, pentobarbital reduced conditioned suppression. In the first experiment (4 rats), this effect was increased by the combination of the specific benzodiazepine antagonist flumazenil (10 mg/kg) with pentobarbital but unaffected by the combination of picrotoxin (1.5 mg/kg) with pentobarbital. In the second experiment (3 rats), this effect was attenuated when picrotoxin (2.0 mg/kg) or Ro5-3663 (5.0 mg/kg) were also administered. These findings add to the data on the effects of anxiolytics and related compounds on conditioned suppression, they provide more information on the possible nature of the GABA/benzodiazepine receptor complex and suggest that flumazenil can have anxiolytic as well as anxiogenic effects.