Possible involvement of NO-cGMP signaling in the antidepressant like Effect of Amantadine in mice.

In the present study, antidepressant like effect of amantadine was studied in mice using tail suspension test (TST) and forced swim test (FST). Further the effect of amantadine treatment on the brain nitrite, glutamate and serotonin levels was also determined. Amantadine (AMT) (50, 100 and 150 mg/kg, i.p.) was administered to the mice and after 30 min of administration the mice were subjected to TST and FST. It was observed that the administration of AMT (100 and 150 mg/kg, i.p.) decreased the immobility period of mice in TST and FST significantly as compared to control. The findings from the whole brain neurochemical assay suggested that the AMT (100 and 150 mg/kg, i.p.) treatment decreased the brain nitrite and glutamate level but increased the brain serotonin significantly as compared to control. Further the influence of NO-cGMP signaling in the antidepressant like effect of amantadine was also determined. It was observed that the NO donor (i.e. L-Arginine (50 mg/kg, i.p.)) potentiated the effect elicited by AMT (50 mg/kg, i.p.) in FST and decreased the brain serotonin level of AMT (50 mg/kg, i.p.) treated mice. Further the pretreatment of cGMP modulator (i.e. Sildenafil (1 mg/kg, i.p.)) potentiated the behavioral effect elicited by AMT (50 mg/kg, i.p.) in TST and FST and decreased the brain nitrite and glutamate level of AMT (50 mg/kg, i.p.) treated mice. In conclusion, amantadine exerted antidepressant like effect in mice and NO-cGMP signaling influences the antidepressant like effect of amantadine in mice.