Enhancement of learning and memory in mice by a benzodiazepine antagonist

Benzodiazepines, a class of drugs widely employed as anxiolytics and anticonvulsants, can induce impairments of learning and memory. The purpose of the present investigation was to determine if a benzodiazepine receptor antagonist, flumazenil (Ro 15-1788), could enhance learning and memory. Pretraining injection of flumazenil (2.5 to 40.0 mg/kg) was found to enhance both learning and memory in a test requiring young mice to discriminate the correct arm of a T-maze to escape mild electric shock. In a second test, which required mice to passively avoid a dark chamber after shock, flumazenil pretreatment prevented the occurrence of amnesia induced by the cholinergic receptor antagonist scopolamine. It is hypothesized that flumazenil may facilitate learning or memory processes by reversing a negative modulatory influence of endogenous diazepam-like ligands for benzodiazepine receptors.