Chronopharmacology of Melatonin: Inhibition by Benzodiazepine Antagonism

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Abstract
We endeavored to determine whether three behavioral effects of melatonin in rodents, i.e., depression of locomotor activity in hamsters, analgesia in mice, and impairment of 3-mercaptopropionic acid (3-MP) convulsions, exhibited the time dependency known to occur for several neuroendocrine effects of the hormone. Activity was monitored and registered by means of an optical acto-meter, and analgesia was assessed by the hot-plate procedure. Locomotor activity, analgesia, and seizure susceptibility were maximal at the beginning of the scoto-phase and minimal at noon. The effects of melatonin on the three parameters peaked at early night. The administration of the benzodiazepine antagonist fluma-zenil, although unable by itself to modify locomotor activity, pain, or seizure threshold, blunted the activity of melatonin. These results suggest that the time-dependent effects of melatonin on specific rodent behaviors may be mediated by central synapses employing 7-aminobutyric acid (GABA) as an inhibitory transmitter.