Depressive-like behavior induced by tumor necrosis factor-α in mice
Depressive-like behavior induced by tumor necrosis factor-α in mice
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DOI：
10.1016/j.neuropharm.2011.08.018
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发表时间：
2012-01-01
影响因子：
4.7
通讯作者：
Rodrigues, Ana Lucia S.
中科院分区：
文献类型：
--
作者：
Kaster, Manuella P.;Gadotti, Vinicius M.;Rodrigues, Ana Lucia S.
促炎细胞因子参与抑郁症的发病机制。然而，很少有关于其对抗抑郁药的反应的特征很好地表征的马槟榔诱导的抑郁症的动物模型可用。因此，本研究的目的是提出一个模型的抑郁样行为诱导的肿瘤坏死因子-α（TNF-α）的管理抗抑郁药治疗的反应。在强迫游泳试验（FST）和悬尾试验（TST）（分别为0.1-1 fg/部位和0.001 fg/部位）中，通过i. c. v.途径给予TNF-α产生抑郁样行为，而不改变旷场试验中的运动活性。此外，抗TNF-α抗体（0.1-1 pg/部位，i. c. v.），而不是TNF-α合成抑制剂沙利度胺（3-30 mg/kg，s.c.）在FST中产生抗抑郁样反应。此外，抗TNF-α抗体（0.01 μ g/部位，i.c.v）或沙利度胺（30 mg/kg，s.c.）逆转TNF-α（0.1 fg/site，i. c. v.）在FST。与野生型小鼠相比，TNF-α受体1（TNFR 1）敲除小鼠在FST和TST中表现出抗抑郁样行为。用氟西汀（32 mg/kg，i.p.）、丙咪嗪（15 mg/kg，i.地昔帕明（16 mg/kg，i.p）可预防TNF-α诱导的抑郁样效应。(0.1 fg/部位，i. c. v.）在FST。此外，TNF-α（0.1 fg/部位，静脉注射）给药在蔗糖摄入试验中产生快感缺乏反应，这可通过抗TNF-α抗体（0.01 μ g/部位，i.c.v）或氟西汀（32 mg/kg，i. p.）预防。两者合计，这些结果表明，TNF-α产生抑郁样状态的小鼠，加强概念，炎症成分可能在抑郁症的病理生理学中发挥重要作用，并建议中央管理的TNF-α可能是一种新的方法来研究抑郁症的炎症成分。(C)2011爱思唯尔有限公司版权所有。
Pro-inflammatory cytokines are implicated in the pathogenesis of depression. However, few animal models of cytokine-induced depression well characterized regarding its response to antidepressants are available. Hence, the aim of this study was to propose a model of depressive-like behavior induced by the administration of tumor necrosis factor-alpha (TNF-alpha) responsive to antidepressant treatments. TNF-alpha administered by i.c.v. route produced a depressive-like behavior in the forced swimming test (FST) and tail suspension test (TST) (0.1-1 fg/site and 0.001 fg/site, respectively), without altering the locomotor activity in the open-field test. In addition, anti-TNF-alpha antibody (0.1-1 pg/site, i.c.v.), but not the inhibitor of TNF-alpha synthesis thalidomide (3-30 mg/kg, s.c.) produced an antidepressant-like response in the FST. Moreover, either anti-TNF-alpha antibody (0.01 pg/site, i.c.v) or thalidomide (30 mg/kg, s.c.) reversed the depressive-like behavior induced by TNF- (0.1 fg/site, i.c.v.) in the FST. TNF-alpha receptor 1 (TNFR1) knockout mice exhibited an antidepressant-like behavior in the FST and in the TST as compared with the wild type mice. Treatment with fluoxetine (32 mg/kg, i.p), imipramine (15 mg/kg, i.p.) and desipramine (16 mg/kg, i.p) prevented the depressant-like effect induced by TNF-alpha. (0.1 fg/site, i.c.v.) in the FST. In addition, TNF-alpha (0.1 fg/site, i.c.v.) administration produced an anhedonic response in a sucrose intake test, which was prevented by anti-TNF-alpha antibody (0.01 pg/site, i.c.v) or fluoxetine (32 mg/kg, i.p). Taken together, these results indicate that TNF-alpha produces a depressive-like state in mice, reinforcing the notion that an inflammatory component may play an important role in the pathophysiology of depression and suggesting that the central administration of TNF-alpha may be a novel approach to study the inflammatory component of depressive disorder.This article is part of a Special Issue entitled 'Anxiety and Depression'. (C) 2011 Elsevier Ltd. All rights reserved.