Involvement of GABAergic systems in benzodiazepine-induced impairment of passive avoidance learning in mice

The possible involvement of GABAergic neuronal systems in benzodiazepine (BZP)-induced impairment of a passive avoidance response was investigated. Chlordiazepoxide (CDP) impaired passive avoidance when administered prior to training. The CDP-induced impairment was antagonized by pretreatment with picrotoxin, but not by pretreatment with bicuculline or post-training administration of picrotoxin. On the contrary, when combined with muscimol, the dose at which CDP impaired the response was lower than the dose at which it did so alone. The synergy of muscimol and CDP was attenuated by pretreatment with flumazenil or bicuculline. From these results, we conclude that GABAergic systems play an important role in the BZP-induced impairment of passive avoidance.