Evidence for the role of nitric oxide in kappa-opiate tolerance in mice.

The hypothesis that inhibition of nitric oxide (NO) synthase with subsequent decrease in the production of NO might attenuate the development of kappa-opiate tolerance was examined. Concurrent treatment of NO synthase inhibitor, NG-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-dependently attenuated the development of tolerance to the analgesic and 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 administration of U-50,488H. A potential role for NO in the development of kappa-opiate tolerance is suggested.