The sleep-inducing effect of ethanol microinjection into the medial preoptic area is blocked by flumazenil

Previous studies have shown that a wide range of sedative/hypnotic agents, including ethanol, induce sleep when microinjected into the medial preoptic area (MPA) of the anterior hypothalamus. The mechanism by which ethanol acts at this site to induce sleep has not been clear, though possibilities include alterations of chloride channel function in the GABA(A)-benzodiazepine receptor complex, or increases in neuronal membrane fluidity. In order to explore the former possibility, we have microinjected into the MPA ethanol 0.24 and 0.47 microM, alone and in combination with the benzodiazepine receptor antagonist flumazenil, which has no effects on membrane fluidity or voltage-dependent calcium channel function. Ethanol microinjections significantly reduced sleep latency, and tended (P<0.06) to increase total sleep time. Flumazenil given by itself had no significant effects on sleep, but when given in combination with both doses of ethanol, blocked its hypnotic effects. These data suggest that the sleep-inducing action of ethanol microinjections into the MPA is mediated by ethanol-induced alteration of GABA(A)-benzodiazepine receptor function.