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 β-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 ( B max) without affecting the dissociation constant ( K D), while melatonin, ineffective in control animals, counteracted the effect of pinealectomy. Intracerebroventricular injection of β-endorphin increases B max in both control and pinealectomized animals, the effect being significantly higher in the latter. Simultaneous i.c.v. injection of melatonin + β-endorphin did not further increase B max in any group, whereas i.c.v. injection of naloxone significantly blocked the effects of melatonin and/or β-endorphin administration. Pineal sympathetic denervation produced a significant increase in B max and K D, whereas i.c.v. injection of melatonin further increased the former, restoring K D to control values. Neither i.c.v. administration of β-endorphin or melatonin + β-endorphin significantly modified the ganglionectomy-dependent increase in B max, although both treatments restored K D to control values. Naloxone administration had no effect on β-endorphin- and melatonin + β-endorphin-treated ganglionectomized groups, but counteracted the increased effect of melatonin on B max in ganglionectomized animals.