Evidence for a role of N-Methyl- d-aspartate receptors in l-arginine-induced attenuation of morphine antinociception

Abstract

Twice daily injections of l-arginine (50, 100 or 200 mg/kg, i.p.) for 4 days dose-dependently, decreased morphine antinociception in male Swiss–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 235959, a competitive antagonist of the NMDA receptor 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 antinociception.