RESUMEN
Clinical and preclinical data reported that ascorbic acid has antidepressant properties. The present study was designed to investigate the participation of l-arginine-NO-cGMP pathway in the antidepressant-like effect of ascorbic acid in the tail suspension test (TST) in mice. The antidepressant-like effect of ascorbic acid (1mg/kg, p.o.) in the TST was prevented by the pre-treatment of mice with NMDA (0.1pmol/site, i.c.v.), l-arginine (750mg/kg, i.p., a substrate for nitric oxide synthase) or sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor). The administration of MK-801 (0.001mg/kg, i.p), 7-nitroindazole (25mg/kg, i.p., a neuronal nitric oxide synthase inhibitor) or ODQ (30pmol/site i.c.v., a soluble guanylate cyclase inhibitor) in combination with a sub-effective dose of ascorbic acid (0.1mg/kg, p.o.) reduced the immobility time in the TST test when compared with either drug alone. None of the results in the TST appears to be due to a nonspecific locomotor effect. Our findings provide evidence that the effect of ascorbic acid in the TST involve an interaction with NMDA receptors and l-arginine-NO-cGMP pathway, contributing to the understanding of the mechanisms underlying the antidepressant-like effect of this vitamin.