The Involvement of Nitric Oxide in Antidepressant-Like Effect of Metformin after Bile-Duct Ligation in NMRI Mice

Background: In some disorders such as diabetes mellitus patients can displaydepressive symptoms. Metformin is among the first-line treatments formanagement of the type 2 diabetes mellitus which may have some antidepressanteffect.Objective: Current investigation was performed to examine the anti-depressanteffects of metformin and the involvement of nitric oxide (NO) in this way, in anexperimental animal model of cholestasis in NMRI (Naval Medical ResearchInstitute) mice.Materials and Methods: Bile duct ligated (BDL) and sham-operated micewere forced to swim separately and the effect of metformin on immobility timein the last 4 minutes of the 6 minutes test was assessed. To evaluate theprobable participation of NO, N-nitro-L-arginine methyl ester (L-NAME) anon-specific NO synthase inhibitor and aminoguanidine, a specific iNOsynthase inhibitor were injected acutely to metformin-treated BDL mice andthen their immobility time was calculated in forced swimming test (FST).Results: The immobility time significantly reduced after bile-duct ligation andmetformin-treatment decreased this time additionally. L-NAME but not aminoguanidineadministration significantly inhibited antidepressant like property ofmetformin in BDL mice. We have displayed that NO overproduction bymetformin in cholestatic mice produce an anti-depressant like effect, causing adecrease in the mice immobility time in FST.Conclusion: Metformin pretreatment can decrease depression in cholestaticmice through an NO dependent pathway.

Keywords:

Metformin , Nitric Oxide , Cholestasis , Antidepressive Agents , Mice