ENDOGENOUS NITRIC-OXIDE MODULATES NALOXONE-PRECIPITATED WITHDRAWAL SIGNS IN A MOUSE MODEL WITH ACUTE CHOLESTASIS

Cholestasis liver disease is associated with clinical and experimental findings consistent with increased opioidergic neuromodulation, incre ased plasma total activity, and elevated plasma enkephalin concentrati ons. The effect of the nitric oxide (NO) synthase inhibitor, L-nitro-a rginine (L-NA, 0.03, 0.1, 0.3, 1 mg/kg), and the nitric oxide precurso r, L-Arg (30 mg/kg), on antinociception induced by bile duct resection or sham operation, as well as on opioid dependence, was examined in m ale albino Swiss mice. Repeated (5 days) administration of L-NA attenu ated signs of dependence, as assessed by naloxone (5 mg/kg)-precipitat ed withdrawal, and decreased the antinociception; however, L-Arg poten tiated withdrawal signs and increased the antinociception. The results of this study support the involvement of the L-arginine/nitric oxide pathway in the opioidergic-dependent manifestation of cholestasis in a n animal model.