MELATONIN AS AN ANXIOLYTIC IN RATS - TIME-DEPENDENCE AND INTERACTION WITH THE CENTRAL GABAERGIC SYSTEM

Anxiolytic and pro-exploratory melatonin properties were assessed in r ats using a plus-maze procedure. Both melatonin (1 mg/kg) and diazepam (0.5 mg/kg) showed a significant diurnal variation to decrease anxiet y and to promote exploratory behavior. Melatonin displayed anxiolytic activity at night, with absence of effects at noon and a weak activity at the beginning of the light phase. Melatonin pro-exploratory activi ty was found only at night. Diazepam exerted significant anxiolysis du ring the night, with less activity during the day. Diazepam pro-explor atory activity was found during the night only. A dose-response study carried out by injecting 1-20 mg/kg melatonin at 12:00 or 18:00 h indi cated that melatonin activity was greatest at 18:00 h. Diazepam was an xiolytic at both times, and pro-exploratory at 18:00 h only. Melatonin activity was blunted by administration of the benzodiazepine antagoni st, flumazenil.