EVIDENCE FOR A ROLE OF N-METHYL-D-ASPARTATE RECEPTORS IN L-ARGININE-INDUCED ATTENUATION OF MORPHINE ANTINOCICEPTION

Twice daily injections of L-arginine (50, 100 or 200 mg/kg, i.p.) for 4 days dose-dependently, decreased morphine antinociception in male Sw iss-Webster mice as measured by the tail-flick test. To determine the possible role of N-methyl-D-aspartate (NMDA) receptor in the action of L-arginine, the effects of MK-801, a noncompetitive antagonist of the NMDA receptor and of LY 23599, a competitive antagonist of the NMDA r eceptor on L-arginine-induced attenuation of morphine antinociception were determined, MK-801 (0.01-0.10 mg/kg, i.p.) or LY 235959 (1.0-4.0 mg/kg, i.p.) given 10 min before each injection of L-arginine (200 mg/ kg, i.p.) reversed the action of the letter in a dose-dependent manner on morphine antinociception. It is concluded that NMDA receptors are involved in the action of L-arginine in attenuating morphine antinocic eption. (C) 1998 Elsevier Science B.V.