Objective Endogenous opioids and nitric oxide (NO) are signalling molecules that play important roles in depressive disorders. Elevated levels of these substances are seen in cholestasis subjects. This study was undertaken to investigate the effect of opioid and nitrergic systems on depression in an experimental model of cholestasis.
Method Bile duct ligated (BDL) and sham-operated mice were forced to swim individually and the immobility time of the last 4 min was evaluated to determine the effect of cholestasis on depression. To assess the possible involvement of endogenous opioids and NO, an antagonist of opioids receptors, naltrexone (20 mg/kg, i.p.), and a non-specific NOS inhibitor, N-nitro-l-arginine methyl ester (L-NAME, 20 mg/kg, i.p.), and sub-effective doses of both of them (3 mg/kg, i.p.) were administrated acutely, one hour before forced swimming test (FST). And chronically, both for 5 and 7 days after operation, to BDL and Sham-operated mice and then were tested by FST.
Results The immobility time significantly decreased after bile duct ligation. naltrexone and L-NAME significantly reversed antidepressant like effect of cholestasis in both 5 and 7 days groups .Co-administration of sub-effective doses of naltrexone and L-NAME also reversed antidepressant effect in FST in chronic administration, and significant difference was observed in immobility times between all 5 and 7 days groups. But acute drug administration did not reverse the anti-depressant effect of cholestasis.
Conclusion We have shown for the first time that elevated levels of endogenous opioids and nitric oxide (NO) due to bile-duct ligation in mice induce an antidepressant like effect, causing a reduction in mice immobility time in FST. The effect was reversed with blockage of nitrergic and opioid systems. And also study showed the predominant effect of opioid system and NO modulation of that in anti-depressant like effect of cholestasis.