MODULATION OF MORPHINE ANTINOCICEPTION IN THE MOUSE BY ENDOGENOUS NITRIC-OXIDE

1 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. 2 N-G-Monomethyl-L-arginine (L-NMMA, 5-50 mg kg(-1) i.p.) and N-G-nitro-L-arginine methyl ester (L-NAME,5-30 mg kg(-1) i.p.), but not N-G-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. 3 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. 4 These results suggest that the L-arginine-nitric oxide pathway plays a modulating role in the morphine-sensitive nociceptive processes.