In order to determine whether the in vitro ability of the pineal indoleamine hormone, melatonin, to modulate binding at the GABA-benzodiazepine receptor complex is operative in vivo we have examined the effects of chronic melatonin administration on 3H-GABA and 3H-diazepam binding in rat brain. Melatonin was injected daily in increasing doses for three weeks and animals were sacrificed at 2 or 26 hours after the final injection. A melatonin-induced enhancement of 3H-GABA binding was observed in both single-point and saturation binding experiments. Scatchard analysis of 3H-diazepam binding revealed a melatonin-induced increase in binding affinity at 26 hours in the forebrain and at 2 hours in the cerebellum with no significant changes in binding site concentration. These findings are consistent with the proposal that melatonin's psychopharmacological effects are due at least in part to its ability to enhance central GABAergic transmission by modulating GABA receptor activity.

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