ABSTRACT
Background: In some disorders such as diabetes mellitus patients can display depressive symptoms. Metformin is among the first-line treatments for management of the type 2 diabetes mellitus which may have some anti-depressant effect
Objective: Current investigation was performed to examine the anti-depressant effects of metformin and the involvement of nitric oxide [NO] in this way, in an experimental animal model of cholestasis in NMRI [Naval Medical Research Institute] mice
Materials and Methods: Bile duct ligated [BDL] and sham-operated mice were forced to swim separately and the effect of metformin on immobility time in the last 4 minutes of the 6 minutes test was assessed
To evaluate the probable participation of NO, N-nitro-L-arginine methyl ester [L-NAME] a non-specific NO synthase inhibitor and aminoguanidine, a specific iNO synthase inhibitor were injected acutely to metformin-treated BDL mice a] then their immobility time was calculated in forced swimming test [FST]
Results: The immobility time significantly reduced after bile-duct ligation ari metformin-treatment decreased this time additionally. L-NAME but not aminoguanidine administration significantly inhibited antidepressant like property of metformin in BDL mice
We have displayed that NO overproduction by metformin in cholestatic mice produce an anti-depressant like effect, causing a decrease in the mice immobility time in FST
Conclusion: Metformin pretreatment can decrease depression in cholestatic mice through an NO dependent pathway