Effects of acute and chronic administration of L-arginine on the antinociceptive action of morphine-6-beta-D-glucuronide.

Chronic administration of L-arginine (200 mg/kg i.p.) but not of D-arginine (200 mg/kg i.p.) twice a day for 4 days decreased the antinociceptive response to subcutaneously administered morphine-6-beta-D-glucuronide (M6G), a potent metabolite of morphine, in male Swiss-Webster mice as measured by the tail-flick test. However, the antinociceptive response to intracerebroventricularly administered M6G was unaffected by chronic treatment with L-arginine. The decreased antinociceptive response to M6G (s.c.) was reversed by concurrent administration of NG-nitro-L-arginine (5 mg/kg i.p.), an inhibitor of nitric oxide synthase. Acute administration of L-arginine (200 mg/kg i.p.) had no effect on M6G-induced antinociception, but higher doses (400 and 800 mg/kg i.p.) decreased it. Since the antinociceptive response to centrally administered M6G was unaffected by chronic L-arginine treatment, the decreased antinociceptive response of peripherally administered M6G may be related to a decrease of M6G entry into brain structures responsible for antinociceptive action.