Chlordiazepoxide enhances the anxiogenic action of CGS 8216 in the social interaction test: evidence for benzodiazepine withdrawal?

Abstract

The benzodiazepine receptor 'inverse agonist' CGS 8216 has a specific anxiogenic action in the social interaction test that cannot be reversed by other compounds acting at the benzodiazepine site: Ro 15-1788, FG 7142 or beta-CCE. We tried to reverse the anxiogenic effect with chlordiazepoxide, which is able to antagonise the anxiogenic effects of several other compounds acting at benzodiazepine or related sites. Chlordiazepoxide given acutely (10-20 mg/kg) was unable to antagonise the anxiogenic action of CGS 8216 (5-10 mg/kg); instead there was a tendency to enhance its effects. The effects of chlordiazepoxide after 5 days pretreatment were then assessed, since chronic treatment is necessary to reverse the anxiogenic actions of Ro 15-1788 and Ro 5-4864. At 5 mg/kg chronically, chlordiazepoxide was unable to antagonise the anxiogenic effect of CGS 8216, and at 20 mg/kg there was a significant enhancement of the effects of CGS 8216 on social interaction without an effect on locomotor activity. These results are discussed in terms of withdrawal from benzodiazepine treatment.