Modulation of morphine antinociception in the mouse by endogenous nitric oxide

Abstract

L‐Arginine (100–1000 mg kg−1) administered orally (p.o.) or intraperitoneally (i.p.), but not intracerebroventricularly (i.c.v., 0.08 mg per mouse), reduced the antinociceptive effect of morphine (0.5–10 mg kg−1 s.c.) assessed in mice using three different tests: hot plate, tail‐flick and acetic acid‐induced writhing. D‐Arginine (up to 1000 mg kg−1 p.o. or i.p.) was ineffective. NG‐Monomethyl‐L‐arginine (L‐NMMA, 5–50 mg kg−1 i.p.) and NG‐nitro‐L‐arginine methyl ester (L‐NAME, 5‐ 30 mg kg−1 i.p.), but not NG‐nitro‐D‐arginine methyl ester (D‐NAME, 30 mg kg−1 i.p.), reversed in all assays the effect of L‐arginine on morphine‐induced antinociception. Morphine (10 mg kg−1 s.c), L‐arginine (1000 mg kg−1 p.o.) or L‐NAME (30 mg kg−1 i.p.), either alone or in combination, did not produce changes in locomotor activity or sensorimotor performance of animals. These results suggest that the L‐arginine‐nitric oxide pathway plays a modulating role in the morphine‐sensitive nociceptive processes. 1994 British Pharmacological Society