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 beta-endorphin, on [3H]flunitrazepam ([3H]FNZ) binding to the rat cerebral cortex of hypophysectomized rats was investigated. Melatonin (10-20 ng), beta-endorphin (10-20 ng), and melatonin + beta-endorphin (10-20 ng of each compound) all increased [3H]FNZ binding to a similar extent and in a dose-related manner. The effects of melatonin (10 ng) on [3H]FNZ binding were prevented by simultaneous injection with the specific opioid antagonist naloxone. Naloxone also blocks, although to a lesser extent, the effects of beta-endorphin and of melatonin + beta-endorphin injections. Moreover, naloxone blocks the hypophysectomy-dependent increase in [3H]FNZ binding. These results implicate the modulation of melatonin-dependent changes on brain benzodiazepine receptors by opioid peptides.