Introduction: The mechanisms of hepatic encephalopathy are not fully understood. Moreover, there is no comprehensive data concerning the effects of nitric oxide (NO) system on anxiolytic-like behaviors induced by bile duct ligation (BDL).

Methods: Male mice weighing 25-30 g were used and anxiety-like behaviors were tested using hole-board task.

Results: The data indicated that cholestasis increased the number of head-dipping but did not alter other aspects of behavior, 7 days after BDL, suggesting an anxiolytic-like response. Furthermore, the results showed that intraperitoneal (i.p.) injection of L-arginine (200 and 250 mg/kg) 15 min before testing induced anxiolytic-like behaviors in the normal animals, 4 and 7 days after BDL (considering that the dose of 200 mg in the normal mice is ineffective but is effective in the BDL mice). On the other hand, injection of L-NAME (35 and 45 mg/kg, i.p.) 15 min before testing induced anxiogenic-like behaviors in the normal animals, 4 and 7 days after BDL (the dose of 35 mg/kg in the normal mice is ineffective but is effective in the BDL mice ). Moreover, injection of ineffective doses of L-NAME (25 and 35 mg/kg, i.p.) 15 min before administration of L-arginine (250 mg/kg, i.p.) and 7 days after BDL, decreased anxiolytic-like behaviors, signi.cantly.

Discussion: Cholestatic mice show anxiolytic-like behaviors suggesting the involvement of the nitric oxide system.