Dual effects of melatonin on barbiturate-induced narcosis in rats

Melatonin affects the circadian sleep/wake cycle, but it is not clear wheth er it may influence drug-induced narcosis. Sodium thiopenthal was administe red intraperitoneally into male rats pre-treated with melatonin (0.05, 0.5, 5 and 50 mg/kg). Melatonin pre-treatment affected in a dual manner barbitu rate narcosis, however, no dose-effect correlation was found. In particular , low doses reduced the latency to and prolonged the duration of barbiturat e narcosis. In contrast, the highest dose of melatonin (50 mg/kg) caused a paradoxical increase in the latency and produced a sustained reduction of t he duration of narcosis, and a reduction in mortality rate. Melatonin 0.5 a nd 5 mg/kg influenced the duration but not the latency of ketamine- or diaz epam-induced narcosis. Thus, the dual action of melatonin on pharmacologica l narcosis seems to be specific for the barbiturate mechanism of action. (C ) 2001 Published by Elsevier Science ireland Ltd.