Evidence of GABAergic modulation in melatonin-induced short-term memory deficits and food consumption

Many of the pharmacological effects of melatonin have been found to be similar to those of benzodiazepines. In the present study, we analyzed the role of melatonin on short-term memory retrieval on transfer latency in elevated plus maze and food consumption behavior, and the effects were compared with those of diazepam. Melatonin dose-dependently (10-100 mg/kg) produced short-term memory deficit and it potentiated diazepam- (1 mg/kg) induced cognitive deficit in mice. Flumazenil (1 and 4 mg/kg) could reverse enhancement in diazepam-induced memory deficit by melatonin. Chronic treatment with melatonin (10 mg/kg/7d) produced a similar profile in transfer latency on elevated plus maze compared with that of diazepam. In a food consumption behavior study, melatonin (25 and 50 mg/kg) produced a significant hyperphagic effect compared to control. Flumazenil (4 mg/kg) could significantly reverse the hyperphagic effects induced by diazepam (2 mg/kg), but would be insignificant with regard to that due to melatonin. These findings provide further evidence that some of the pharmacological effects of melatonin are comparable with those of diazepam and may involve central GABAergic mechanism.