Modulation of morphine antinociception in the mouse by endogenous nitric oxide

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Abstract
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 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. 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.