REVERSAL OF TRIAZOLAM-INDUCED AND ZOLPIDEM-INDUCED MEMORY IMPAIRMENT BY FLUMAZENIL

The effects of flumazenil, a benzodiazepine receptor antagonist, on tr iazolam- and zolpidem-induced memory impairment were investigated. Six ty subjects received oral triazolam 0.5 mg, zolpidem 20.0 mg, or place bo at 10 a.m. (n = 20 per drug). Ninety minutes later, half of the sub jects (n = 10) in each oral drug group were administered flumazenil 1. 0 mg, while the remaining half received placebo (normal saline), throu gh indwelling venous catheters. Learning/memory tests (including Simul ated Escape, Restricted Reminding, Paired-Associates, and Repeated Acq uisition) were administered at that time, and at 1.5-h intervals over the next 6 h. Triazolam/placebo and zolpidem/placebo drug combinations impaired memory on all tests (all Ps < 0.05). However, the triazolam/ flumazenil and zolpidem/flumazenil groups showed no evidence of impair ment during any test session. These results demonstrate that flumazeni l 1.0 mg rapidly and lastingly reverses memory impairment caused by ag onists of the benzodiazepine receptor. Furthermore, nonsignificant tre nds suggested that performance of the placebo/flumazenil group was con sistently better than that of the placebo/placebo group, denoting a po ssible role of endogenous benzodiazepine agonists in natural sleep/wak e processes.