Reversal of alcohol-induced amnesia by the benzodiazepine inverse agonist Ro 15-4513

We investigated the effects of benzodiazepine inverse agonists on ethanol-induced amnesia using a passive avoidance task. Pretraining treatment of mice with ethanol significantly impaired the passive avoidance response: there was a significant reduction in the % retention and step-down latency. The benzodiazepine inverse agonists, Ro 15-4513 and β-CCM, significantly increased the % retention and prolonged the step-down latencies in mice treated with ethanol, but FG 7142 did not. The anti-amnesic effect of Ro 15-4513 were completely antagonized by co-administration of Ro 15-1788, a benzodiazepine antagonist. These results suggest that the anti-amnesic effect of Ro 15-4513 on alcohol-induced amnesia is mediated by benzodiazepine receptors.