RECIPROCAL EFFECTS OF CHRONIC DIAZEPAM AND MELATONIN ON BRAIN MELATONIN AND BENZODIAZEPINE BINDING-SITES

Recent reports indicate that benzodiazepines can suppress melatonin le vels 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. Da ily injections (3 weeks) of diazepam markedly reduced I-125-melatonin binding site density in the medulla-pons but not cortex of male rats, whereas benzodiazepine binding was not significantly affected. Melaton in, administered via the drinking water, significantly enhanced benzod iazepine (H-3-RO 15-1788) binding in the medulla-pons and slightly red uced it in the cortex, but did not affect I-125-melatonin binding. Dia zepam and melatonin combination reversed the suppression by diazepam o f I-125-melatonin binding in the medulla-pons and the suppression by m elatonin of benzodiazepine (H-3-RO 15-1788 and H-3-flunitrazepam) bind ing in the cerebral cortex. These results indicate benzodiazepine-medi ated suppression of brain melatonin binding sites that can be abrogate d by melatonin administration.