Selective MT2 melatonin receptor antagonist blocks melatonin-induced antinociception in rats

The present study was undertaken to assess the effects of intracerebroventricular (i.c.v.) luzindole (a selective MT2 melatonin receptor antagonist) and prazosin (a selective MT3 melatonin receptor antagonist) on melatonin-induced antinociception, so as to clarify which of melatonin receptor subtypes within the central nervous system (CNS) was mediating antinociception. The pain threshold of rats was measured by the hot water (50 degrees C) tail-flick test. It was found that intraperitoneal (i.p.) melatonin (30, 60, 120 mg/kg) resulted in a dose-dependent antinociception. Luzindole (50, 100 mu g) administered intracerebroventricularly antagonized significantly the antinociceptive effect induced by i.p. melatonin (120 mg/kg), whereas prazosin (50 mu g) did not. Neither luzindole (100 mu g, i.c.v.) nor prazosin (50 mu g, i.c.v.) affected the nociceptive threshold when given alone. The results suggest that melatonin-induced antinociception is mediated through the MT2 melatonin receptor subtype within the CNS. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.