Reciprocal effects of chronic diazepam and melatonin on brain melatonin and benzodiazepine binding sites

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Abstract
Recent reports indicate that benzodiazepines can suppress melatonin levels and that melatonin can increase brain benzodiazepine binding. We have studied the possibility of reciprocal effects of chronic diazepam and melatonin on brain melatonin and benzodiazepine binding sites. Daily injections (3 weeks) of diazepam markedly reduced 125I‐melatonin binding site density in the medulla‐pons but not cortex of male rats, whereas benzodiazepine binding was not significantly affected. Melatonin, administered via the drinking water, significantly enhanced benzodiazepine (3H‐RO 15‐1788) binding in the medulla‐pons and slightly reduced it in the cortex, but did not affect 125I‐melatonin binding. Diazepam and melatonin combination reversed the suppression by diazepam of 125I‐melatonin binding in the medulla‐pons and the suppression by melatonin of benzodiazepine (3H‐RO 15‐1788 and 3H‐flunitrazepam) binding in the cerebral cortex. These results indicate benzodiazepine‐mediated suppression of brain melatonin binding sites that can be abrogated by melatonin administration.