Inhibition by lithium of opioid withdrawal-like syndrome and physical dependency in a model of acute cholestasis in mice

Because of the claim that chronic cholestatic liver disease is associated with increased opioidergic tone and that lithium (Li+) inhibits physical dependency in morphine-dependent mice, the effects of chronic Li+ treatment on naloxone-precipitated withdrawal-like syndrome and antinociception were evaluated in an animal model of cholestasis. For this purpose, acute cholestasis was induced by bile duct ligation in mice. The treated group of mice was given lithium chloride (300 mg/l) as drinking fluid for 10–12 days before surgery and 5 days after surgery. Physical 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 present study revealed that chronic Li+ administration significantly reduced the withdrawal-like signs, whereas the antinociception assessed by tail-flick test was not observed in the control group of cholestatic mice. Serum Li+ level in this study was much lower than the commonly accepted therapeutic range. Lithium and opioid agonist ligands have diverse effects on transmembrane signal control systems. So the interaction of Li+ and opioid agonists observed in this study might also be through these systems.