EVIDENCE FOR THE ROLE OF NITRIC-OXIDE IN KAPPA-OPIATE TOLERANCE IN MICE

The hypothesis that inhibition of nitric oxide (NO) synthase with subs equent decrease in the production of NO might attenuate the developmen t of kappa-opiate tolerance was examined. Concurrent treatment of NO s ynthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA) (2-8 mg/kg, i.p .) along with U-50,488H (25 mg/kg, i.p.) twice daily for 4 days dose-d ependently attenuated the development of tolerance to the analgesic an d hypothermic effects of U-50,488H (25 mg/kg, i.p.). L-NMMA by itself did not modify the analgesic and hypothermic effects of acute administ ration of U-50,488H. A potential role for NO in the development of kap pa-opiate tolerance is suggested.