Effects of chlordiazepoxide and putative anxiogenics on conditioned suppression in rats

This paper reports two experiments. In Experiment 1, the effects of chlordiazepoxide alone and in combination with a series of putative antagonists at various sites on the GABA/benzodiazepine receptor complex on conditioned suppression of operant behavior in rats were assessed. Response rates during presentation of a stimulus associated with shock (CS responding) and when only positive reinforcement is effective (pre-CS responding) were analysed. Chlordiazepoxide (10 mg/kg) significantly increased CS responding. This effect was significantly antagonised by Ro15-1788 (10 mg/kg) and by picrotoxin (1.5 mg/kg), but not by bicuculline (1.5 mg/kg) or by delta-amino-n-valeric acid (10 or 20 mg/kg). Chlordiazepoxide also significantly, albeit more slightly, increased pre-CS responding and mone of the other drugs tested significantly antagonised this action, though Ro15-1788 plus chlordiazepoxide resulted in pre-CS response rates not significantly different from either chlordiazepoxide alone or control. These interactions are discussed in the context of the proposed GABA/benzodiazepine receptor complex with the conclusion that drug effects at the benzodiazepine- and picrotoxin-sensitive channel sites have an important role in mediating anxiolytic action. However, behavioral evidence of an important role for GABAa or GABAb receptors remains very limited. The second experiment studied the intrinsic actions of bicuculline, picrotoxin, and Ro15-1788 on conditioned suppression. Responding during a conditioned stimulus associated with a mild (0.125 to 0.15 mA) electric shock (CS responding) and a control rate of responding (pre-CS responding) were recorded. Bicuculline (1.5 mg/kg) and Ro15-1788 (10 mg/kg) did not significantly affect either response rate. Picrotoxin (1.5 mg/kg) significantly reduced both response rates. These results are discussed in the context of drug interaction studies with these compounds and of animal paradigms for the detection of anxiogenic drug effects.