RT Journal Article SR Electronic T1 Mechanism of Attenuation of Morphine Antinociception by Chronic Treatment with l-Arginine JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 707 OP 712 VO 281 IS 2 A1 Bhargava, Hemendra N. A1 Bian, Jing-Tan A1 Kumar, Shailendra YR 1997 UL http://jpet.aspetjournals.org/content/281/2/707.abstract AB The effects of twice-daily injections of l-arginine ord-arginine (200 mg/kg i.p.) for 4 days on morphine-induced antinociception, brain nitric oxide synthase activity and brain and serum distribution of morphine and brain μ-opioid receptors labeled with [3H][d-Ala2,MePhe4,Gly5-ol]enkephalin were determined in male Swiss-Webster mice. Chronic treatment withl-arginine, but not d-arginine, decreased the antinociceptive response to morphine in mice, increased the activity of nitric oxide synthase in the midbrain and decreased brain levels of morphine, compared with vehicle-injected controls. Significant decreases in morphine levels were observed in midbrain, pons and medulla, hippocampus, striatum and spinal cord ofl-arginine-treated mice, in comparison with vehicle-injected mice. However, the levels of morphine in cortex, amygdala and hypothalamus of l-arginine- ord-arginine-treated mice did not differ from those of vehicle-injected controls. Acute treatment with l-arginine (200 mg/kg i.p.) or d-arginine (200 mg/kg i.p.) did not modify either morphine antinociception or morphine distribution in brain regions or the spinal cord. Chronic administration ofl-arginine or d-arginine did not alter theB max or K d values of [3H][d-Ala2,MePhe4,Gly5-ol]enkephalin binding to the mouse brain membranes. These results suggest that chronic treatment with l-arginine reduces the antinociceptive effect of morphine by increasing brain nitric oxide synthase activity and by decreasing the concentration of morphine in certain brain regions and spinal cord. The American Society for Pharmacology and Experimental Therapeutics