INHIBITION BY LITHIUM OF OPIOID WITHDRAWAL-LIKE SYNDROME AND PHYSICALDEPENDENCY IN A MODEL OF ACUTE CHOLESTASIS IN MICE

Because of the claim that chronic cholestatic liver disease is associa ted with increased opioidergic tone and that lithium (Li+) inhibits ph ysical dependency in morphine-dependent mice, the effects of chronic L i+ treatment on naloxone-precipitated withdrawal-like syndrome and ant inociception were evaluated in an animal model of cholestasis. For thi s purpose, acute cholestasis was induced by bile duct ligation in mice . The treated group of mice was given lithium chloride (300 mg/l) as d rinking fluid for 10-12 days before surgery and days after surgery. Ph ysical dependency was observed by precipitating an abstinence syndrome with naloxone (4 mg/kg, s.c.) 5 days after induction of cholestasis. Antinociception was assessed by tail-flick latency test in control and treated groups before administration of naloxone. Results of the pres ent study revealed that chronic Li+ administration significantly reduc ed the withdrawal-like signs, whereas the antinociception assessed by tail-flick test was not observed in the control group of cholestatic m ice. Serum Li+ level in this study was much lower than the commonly ac cepted therapeutic range. Lithium and opioid agonist ligands have dive rse effects on transmembrane signal control systems. So the interactio n of Li+ and opioid agonists observed in this study might also be thro ugh these systems. (C) 1998 John Wiley & Sons, Ltd.