Melatonin enhances antinociceptive effects of δ-, but not μ-opioid agonist in mice

This present study examines the effect of melatonin on antinociceptive action induced by opioid agonists in mice using the tail-flick test. When injected either by intraperitoneal (i.p.) (1, 5, 25 mg/kg) or by intracerebroventricular (i.c.v.) (0.25, 0.5, 1 mg/kg) routes, melatonin significantly enhanced the δ-opioid agonist deltorphin I induced antinociception, but not μ-opioid agonist endomorphin-1. Further investigation showed that i.c.v. luzindole (0.5 mg/kg) (an antagonist of melatonin receptor) significantly antagonized the enhanced antinociceptive effect of i.c.v. melatonin. These results demonstrated that melatonin can specifically enhance the antinociception induced by specific opioid receptor agonist (i.e., δ opioid agonist) acting on melatonin receptor and that melatonin may have augmentation effect on analgesia with delta-, but not mu-opioid agonists in mice.