Chlordiazepoxide enhances the anxiogenic action of CGS 8216 in the social interaction test: evidence for benzodiazepine withdrawal?
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.
D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001570:Benzodiazepinones / Q000008:administration & dosage; D002243:Carbolines / Q000008:administration & dosage; D002707:Chlordiazepoxide / Q000008:administration & dosage* / Q000009:adverse effects; D005442:Flumazenil; D006801:Humans; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage*; D051381:Rats; D012919:Social Behavior; D013045:Species Specificity; D013375:Substance Withdrawal Syndrome
D001570:Benzodiazepinones; D002243:Carbolines; D011720:Pyrazoles; D005442:Flumazenil; C035874:FG 7142; D002707:Chlordiazepoxide; C024915:beta-carboline-3-carboxylic acid ethyl ester; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one