Antidepressant-like effect of α-tocopherol in a mouse model of depressive-like behavior induced by TNF-α

Taking into account that pro-inflammatory cytokines and oxidative and nitrosative stress are implicated in the pathogenesis of depression and that alpha-tocopherol has antidepressant, anti-inflammatory and antioxidant properties, this study investigated the ability of alpha-tocopherol to abolish the depressive-like behavior induced by i.c.v. administration of TNF-alpha in the mouse TST. Additionally, we investigated the occurrence of changes in the levels of Bcl2 and Bax and phosphorylation of GSK-3 beta (Ser9) in the hippocampus of mice. The administration of TNF-alpha (0.001 fg/site, i.c.v.) increased the immobility time in the TST, which was prevented by the administration of alpha-tocopherol at the doses of 10, 30 and 100 mg/kg (p.o.). Subeffective doses of alpha-tocopherol (10 mg/kg, p.o.) and/or the antidepressants fluoxetine (5 mg/kg, p.o.), imipramine (0.1 mg/kg, p.o.) and bupropion (1 mg/kg, p.o.), the NMDA receptor antagonist MK-801 (0.001 mg/kg, p.o.) or the neuronal nitric oxide synthase inhibitor 7-nitroindazole (25 mg/kg, i.p.) prevented the depressive-like effect induced by TNF-alpha. None of the treatments altered the locomotor activity of mice. Treatment with TNF-alpha and/or alpha-tocopherol did not alter the levels of Bax and Bcl2 or the phosphorylation of GSK-3 beta in the hippocampus of mice. Together, our results show a synergistic antidepressant-like effect of alpha-tocopherol with antidepressants against the depressive-like behavior induced by an inflammatory insult, suggesting that this vitamin may be useful to optimize conventional pharmacotherapy of depression, including depressive states associated with inflammatory conditions. (C) 2013 Elsevier Inc. All rights reserved.