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

详细信息    查看全文

• 作者：Luana M. Manosso ; Vivian B. Neis ; Morgana Moretti ; Juliana F. Daufenbach ; Andiara E. Freitas ; Andr¨¦ R. Colla ; Ana L¨²cia S. Rodrigues
• 关键词：CNS ; central nervous system ; FST ; forced swimming test ; GSK-3 ; glycogen synthase kinase-3 ; IFN ; interferon ; IL ; interleukin ; i.c.v. ; intracerebroventricular ; i.p. ; intraperitoneal ; NMDA ; N-methyl-d-aspartate ; NO ; nitric oxide ; nNOS ; neuronal nitric oxide
• 刊名：Progress in Neuro-Psychopharmacology and Biological Psychiatry
• 出版年：2013
• 出版时间：1 October, 2013
• 年：2013
• 卷：46
• 期：Complete
• 页码：48-57
• 全文大小：1166 K

文摘

Taking into account that pro-inflammatory cytokines and oxidative and nitrosative stress are implicated in the pathogenesis of depression and that ¦Á-tocopherol has antidepressant, anti-inflammatory and antioxidant properties, this study investigated the ability of ¦Á-tocopherol to abolish the depressive-like behavior induced by i.c.v. administration of TNF-¦Á in the mouse TST. Additionally, we investigated the occurrence of changes in the levels of Bcl2 and Bax and phosphorylation of GSK-3¦Â (Ser9) in the hippocampus of mice. The administration of TNF-¦Á (0.001 fg/site, i.c.v.) increased the immobility time in the TST, which was prevented by the administration of ¦Á-tocopherol at the doses of 10, 30 and 100 mg/kg (p.o.). Subeffective doses of ¦Á-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-¦Á. None of the treatments altered the locomotor activity of mice. Treatment with TNF-¦Á and/or ¦Á-tocopherol did not alter the levels of Bax and Bcl2 or the phosphorylation of GSK-3¦Â in the hippocampus of mice. Together, our results show a synergistic antidepressant-like effect of ¦Á-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.