Possible involvement of NO-sGC-cGMP signaling in the antidepressant like effect of pyridoxine in mice.

The present study was designed to determine the antidepressant like effect of pyridoxine in mice. Pyridoxine (12.5, 25 and 50 mg/kg, i.p.) was administered to the mice and depression related behavioral and neurochemical alterations were determined. It was observed that pyridoxine (50 mg/kg, i.p.) treatment decreased the immobility period in tail suspension test (TST) and forced swim test (FST) significantly as compared to control. Pyridoxine (50 mg/kg, i.p.) treatment increased the level of serotonin (5-HT) and decreased the level of nitrite in the brain of mice significantly as compared to control. Pyridoxine thus confer antidepressant like effect by increasing the level of 5-HT and by decreasing the level of nitrite in the brain of mice. Further the influence of nitric oxide (NO)/ soluble guanylate cyclase (sGC)/ cyclic guanosine monophosphate (cGMP) in antidepressant-like effect of pyridoxine was studied. It was observed that the pretreatment of NO donor (i.e. L-Arginine) and cGMP modulator (i.e. sildenafil) counteracted while the pretreatment of NO/sGC inhibitor (i.e. methylene blue) potentiated the effect of pyridoxine in TST and FST. Pretreatment of NO donor did not influence, pretreatment of NO/sGC inhibitor decreased while the pretreatment of cGMP modulator increased the level of brain nitrite in pyridoxine treated mice. Further the pretreatment of NO donor and cGMP modulator decreased while the pretreatment of NO/sGC inhibitor increased the level of brain serotonin in pyridoxine treated mice. Pyridoxine thus exerted antidepressant like effect and NO-sGC-cGMP signaling modulated the antidepressant like effect of pyridoxine in mice.