Antidepressant Like Effect of Ascorbic Acid in Mice: Possible Involvement of NO-sGC-cGMP Signaling

The present study was designed to determine the antidepressant like activity of ascorbic acid (AA) in mice. Further the influence of NO-sGC-cGMP signaling in the antidepressant like effect of AA in mice was determined. Male swiss albino mice were used in the present study. Mice in the control group received saline and fluoxetine (10 mg/kg, i.p.) was used as the standard antidepressant drug. AA (50, 100 and 150 mg/kg, i.p.) was administered to the mice and depression related behavior were determined using tail suspension test (TST) and forced swim test (FST). Further the whole brain nitrite and serotonin levels were also determined. It was observed that the administration of AA (100 mg/kg, i.p.) reversed the depression like behavior in mice in TST and FST. AA (100 mg/kg, i.p.) treatment decreased the level of nitrite and increased the level of serotonin in the brain of mice significantly as compared to control. Further the behavioral and neurochemical effect of AA (50 mg/kg, i.p) was studied in NO modulator [NO donor: L-Arginine (50 mg/kg, i.p); NO-sGC inhibitor: methylene blue (1 mg/kg, i.p.) and cGMP modulator: sildenafil (1 mg/kg, i.p.)] pretreated mice. It was observed that the pretreatment of NO donor and cGMP modulator counteracted the effect conferred by AA (50 mg/kg, i.p). While the pretreatment of NO-sGC inhibitor potentiated the effect conferred by AA (50 mg/kg, i.p). The present study suggested that the AA confer antidepressant like effect in mice and NO-sGC-cGMP signaling pathway influence the antidepressant like effect of AA in mice.