Melatonin exerts an antidepressant-like effect in the tail suspension test in mice: evidence for involvement of N-methyl-D-aspartate receptors and the L-arginine-nitric oxide pathway.

This study investigated the effect of melatonin in the mouse tail suspension test (TST), and the contribution of N-methyl-D-aspartate (NMDA) receptors and the L-arginine-nitric oxide (NO) pathway to its antidepressant-like effect. The immobility time in the TST was reduced by melatonin given either by intraperitoneal (0.1-30 mg/kg) or intracerebroventricular (0.001-0.1 nmol/site) route. The anti-immobility effect of melatonin (1 mg/kg, intraperitoneal, i.p.) was prevented by pre-treatment with guanosine 5'-monophosphate (GMP), ascorbic acid, L-arginine or S-nitroso-N-acetyl-penicillamine, but not with D-arginine. Pre-treatment with melatonin (100 mg/kg, i.p.) prevented the anti-immobility effect of MK-801, ketamine or zinc chloride, but did not alter the effect of imipramine. Furthermore, a sub-effective dose of melatonin (0.001 mg/kg, i.p.) produced a synergistic antidepressant-like effect with MK-801, ketamine, zinc chloride and imipramine in the TST. Taken together these data indicate that the effect of melatonin in the TST seems to be mediated through an interaction with NMDA receptors and the L-arginine-NO pathway.