BENZODIAZEPINE RECEPTOR-MEDIATED BEHAVIORAL-EFFECTS OF NITROUS-OXIDE IN THE RAT SOCIAL-INTERACTION TEST

The present study was conducted to ascertain whether an anxiolytic eff ect of nitrous oxide was demonstrable in rats using the social interac tion test and whether this drug effect might be mediated by benzodiaze pine receptors. Compared to behavior of vehicle-pretreated, room air-e xposed rats, rat pairs exposed to nitrous oxide showed a generally inv erted U-shaped dose-response curve with the maximum increase in social interaction encounters occurring at 25% and significant increase in t ime of active social interaction at 15-35%; higher concentrations prod uced a sedative effect that reduced social interaction. Treatment with 5.0 mg/kg of the anxiolytic benzodiazepine chlordiazepoxide also incr eased social interaction. Pretreatment with 10 mg/kg of the benzodiaze pine receptor blocker flumazenil, which alone had no effect, significa ntly antagonized the social interaction-increasing effects of both nit rous oxide and chlordiazepoxide. In summary, these findings suggest th at nitrous oxide produces a flumazenil-sensitive effect comparable to that of chlordiazepoxide and implicate central benzodiazepine mechanis ms in mediation of the anxiolytic effect of nitrous oxide.