Effect of NMDA receptor antagonist on naloxone‐precipitated withdrawal signs in cholestatic mice

The ability of NMDA antagonist MK-801 to block the expression of opioid-like withdrawal signs was examined in bile duct-ligated mice and the signs were compared with sham operated and unoperated animals. Administration of MK-801 (0/1 mg/kg), 10 min prior to naloxone challenge, significantly reduced the investigated withdrawal signs (jumping, diarrhoea, grooming and climbing) in bile duct-ligated animals. Chronic administration (five consecutive days) of MK-801 (0/1 mg/kg) also decreased all the withdrawal signs in the experimental animals. In an independent series of experiments, the effect of acute and chronic administration of MK-801 on tail-flick latency was investigated in bile duct-ligated animals. Pretreatment with the drug significantly decreased the antinociception induced by bile duct ligation in the mice. The results of this study support evidence for the involvement of the NMDA receptor in yopioidergic-dependent manifestations in a model of obstructive cholestasis. Copyright © 2000 John Wiley & Sons, Ltd.