IDENTIFICATION OF OPIOID RECEPTOR SUBTYPES IN ANTINOCICEPTIVE ACTIONSOF SUPRASPINALLY-ADMINISTERED MITRAGYNINE IN MICE

Mitragynine (MG), a major alkaloidal constituent extracted from the pl ant Mitragyna speciosa Korth, is known to exert an opioid-like activit y. Our previous study showed the involvement of opioid systems in the antinociceptive activity of MG in the tail-pinch and hot-plate tests i n mice. In the present study, to clarify the opioid receptor subtypes involved in the antinociceptive action of MG, we investigated the effe cts of selective antagonists for mu-, delta- and kappa- opioid recepto rs on antinociception caused by the intracerebroventricular (i.c.v.) i njection of MG in the tail-pinch and hot-plate tests in mice. The coad ministration of a selective mu-opioid antagonist, cyprodime (1-10 mu g , i.c.v.) and the pretreatment with a selective mu 1-opioid antagonist naloxonazine (1-3 mu g, i.c.v.) significantly antagonized the antinoc iceptive activities of MG (10 mu g, i.c.v.) and morphine (MOR, 3 mu g, i.c.v.) in the tail-pinch and hot-plate tests. Naltrindole (1-5 ng, i .c.v.), a selective delta-opioid antagonist, also blocked the effects of MG (10 mu g, i.c.v.) without affecting MOR (3 mu g, i.c.v.) antinoc iception. Nor-binaltorphimine, a selective kappa-opioid antagonist, si gnificantly attenuated MG(10 mu g, i.c.v.) antinociception in the tail -pinch test but not in the hot-plate test at the dose (1 mu g, i.c.v.) that antagonized the antinociceptive effects of the selective kappa-o pioid agonist U50,488H in both tests, while it had no effect on MOR an tinociception in either tests. These results suggest that antinocicept ion caused by i.c.v. MG is dominantly mediated by mu- and delta-opioid receptor subtypes, and that the selectivity of MG for the supraspinal opioid receptor subtypes differs from that of MOR in mice.