CGS 8216, a benzodiazepine receptor antagonist, enhances learning and memory in mice

Mice pretreated with the benzodiazepine antagonist, CGS 8216 (2.5, 10, or 40 mg/kg, i.p.) learned a T-maze discrimination to a fixed performance criterion more rapidly than vehicle-treated mice. In retention tests conducted one week later, the drug-treated groups had better first-trial recall and greater difficulty reversing the previously trained maze habit when compared with controls, suggesting improved memory for the previously trained maze habit. The enhanced acquisition and retention following CGS 8216 was similar to that observed previously with another benzodiazepine antagonist, flumazenil (Ro 15-1788). It is postulated that CGS 8216 and flumazenil could act at benzodiazepine receptors to antagonize a tonic inhibitory influence of endogenous, diazepam-like, benzodiazepine receptor ligands on memory processes.