N(G)-nitro-L-arginine reverses L-arginine induced changes in morphine antinociception and distribution of morphine in brain regions and spinal cord of the mouse.

Twice daily injections of L-arginine (200 mg/kg, i.p.), a precursor for nitric oxide (NO), for 4 days decreased morphine antinociception in male Swiss-Webster mice. Chronic treatment with L-arginine also produced significant decreases in morphine levels in midbrain, pons and medulla, hippocampus, corpus striatum and spinal cord of mice following an injection of morphine (10 mg/kg, s.c.) in comparison to vehicle-injected mice. N(G)-nitro-L-arginine (L-NNA), an inhibitor of NO synthase (NOS), (5 mg/kg, i.p.) given prior to each injection of L-arginine reversed the effects of the latter on morphine antinociception and decreases in morphine levels in brain regions and spinal cord. Chronic injections of L-NNA alone did not modify either morphine antinociception or morphine distribution in brain regions and spinal cord of mice. These results suggest that decreases in morphine antinociception by chronic treatment with L-arginine is related to the decreases in the entry of morphine in the central sites. The reversal of L-arginine-induced effects by L-NNA suggests that NO-NOS system may be playing a critical role in the regulation of blood-brain barrier to morphine.