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

作者：Manosso Luana M; Neis Vivian B; Moretti Morgana; Daufenbach Juliana F; Freitas Andiara E; Colla Andre R; Rodrigues Ana Lucia S^*

来源：Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2013, 46: 48-57.

DOI：10.1016/j.pnpbp.2013.06.012

• Antidepressant
• Inflammation
• Tail suspension test
• alpha-Tocopherol

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.

• 出版日期2013-10-1