Melatonin counteracts pinealectomy-dependent decreases in rat brain [3H]flunitrazepam binding through an opioid mechanism.

The effect of intracerebroventricular (i.c.v.) injection of melatonin and/or beta-endorphin on the [3H]flunitrazepam binding sites in the cerebral cortex of pinealectomized or superior cervical ganglionectomized rats was studied. Pinealectomy decreased the maximum concentration of benzodiazepine receptors (Bmax) without affecting the dissociation constant (KD), while melatonin, ineffective in control animals, counteracted the effect of pinealectomy. Intracerebroventricular injection of beta-endorphin increases Bmax in both control and pinealectomized animals, the effect being significantly higher in the latter. Simultaneous i.c.v. injection of melatonin + beta-endorphin did not further increase Bmax in any group, whereas i.c.v. injection of naloxone significantly blocked the effects of melatonin and/or beta-endorphin administration. Pineal sympathetic denervation produced a significant increase in Bmax and KD, whereas i.c.v. injection of melatonin further increased the former, restoring KD to control values. Neither i.c.v. administration of beta-endorphin or melatonin + beta-endorphin significantly modified the ganglionectomy-dependent increase in Bmax, although both treatments restored KD to control values. Naloxone administration had no effect on beta-endorphin- and melatonin + beta-endorphin-treated ganglionectomized groups, but counteracted the increased effect of melatonin on Bmax in ganglionectomized animals.