Intracerebroventricular injection of naloxone blocks melatonin-dependent brain [3H]flunitrazepam binding

THE pineal hormone melatonin modulates the brain benzodiazepine binding sites and its circadian rhythm. In the present study the effects of intracerebroventricular (i.c.v.) administration of naloxone (10–20 ng), alone or in association with melatonin and/or -endorphin, on [H]flunitrazepam ([H]FNZ) binding to the rat cerebral cortex of hypophysectomized rats was investigated. Melatonin (10–20 ng), β-endorphin (10–20 ng), and melatonin + β-endorphin (10–20 ng of each compound) all increased [H]FNZ binding to a similar extent and in a dose-related manner. The effects of melatonin (10 ng) on [H]FNZ binding were prevented by simultaneous injection with the specific opioid antagonist naloxone. Naloxone also blocks, although to a lesser extent, the effects of β-endorphin and of melatonin + β-endorphin injections. Moreover, naloxone blocks the hypophysectomy-dependent increase in [H]FNZ binding. These results implicate the modulation of melatonin-dependent changes on brain benzodiazepine receptors by opioid peptides.