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, increased plasma total activity, and elevated plasma enkephalin concentrations. The effect of the nitric oxide (NO) synthase inhibitor, L-nitro-arginine (L-NA, 0.03, 0.1, 0.3, 1 mg/kg), and the nitric oxide precursor, L-Arg (30 mg/kg), on antinociception induced by bile duct resection or sham operation, as well as on opioid dependence, was examined in male albino Swiss mice. Repeated (5 days) administration of L-NA attenuated signs of dependence, as assessed by naloxone (5 mg/kg)-precipitated withdrawal, and decreased the antinociception; however, L-Arg potentiated 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 an animal model.
Dehpour
A R
AR
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran.
Akbarloo
N
N
Ghafourifar
P
P
D000208:Acute Disease; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001652:Bile Ducts / Q000502:physiology; D002779:Cholestasis / Q000523:psychology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D019335:Nitroarginine; D009569:Nitric Oxide; D009270:Naloxone; D001120:Arginine; D019001:Nitric Oxide Synthase