Voluntary exercise produces antidepressant and anxiolytic behavioral effects in mice
Voluntary exercise produces antidepressant and anxiolytic behavioral effects in mice
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DOI：
10.1016/j.brainres.2007.12.047
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发表时间：
2008-03-14
期刊：
影响因子：
2.9
通讯作者：
Duman, Ronald S.
中科院分区：
文献类型：
--
作者：
Duman, Catharine H.;Schlesinger, Lee;Duman, Ronald S.
关于运动对人类心理健康有益影响的报告越来越多地得到基础研究的支持。运动被假设为调节抗抑郁相关的机制，因此，我们的特点是长期运动的影响，在小鼠的行为范式相关的抗抑郁作用。自由接触转轮的小鼠在习得性无助、强迫游泳（FST）和悬尾范式中表现出抗抑郁样行为。这些反应与抗抑郁药物给药动物的反应相似。当在运动活动没有改变的条件下进行测试时，与久坐不动的对照小鼠相比，运动小鼠也表现出减少的焦虑。原位杂交结果显示，跑轮后海马特定亚区BDNF mRNA表达增加。我们选择了一个范例，FST，在其中调查脑源性神经营养因子（BDNF）在运动行为反应中的功能作用。我们测试了在FST中缺失BDNF基因的杂合子小鼠在轮跑后。运动野生型小鼠在FST中表现出预期的抗抑郁样行为反应。但运动对改善杂合子BDNF基因敲除小鼠的FST表现无效。使用特异性MEK抑制剂PD184161阻断MAPK信号通路，研究了运动小鼠中BDNF信号通路对FST表现的可能功能贡献。对运动小鼠亚慢性给予PD 184161可阻断FST中溶媒处理的运动小鼠中观察到的抗抑郁药样行为反应。总之，小鼠慢性轮跑运动导致抗抑郁样行为变化，可能涉及与抗抑郁药物治疗假设相似的BDNF相关机制。
Reports of beneficial effects of exercise on psychological health in humans are increasingly supported by basic research studies. Exercise is hypothesized to regulate antidepressantrelated mechanisms and we therefore characterized the effects of chronic exercise in mouse behavioral paradigms relevant to antidepressant actions. Mice given free access to running wheels showed antidepressant-like behavior in learned helplessness, forced-swim (FST) and tail suspension paradigms. These responses were similar to responses of antidepressant drug-treated animals. When tested under conditions where locomotor activity was not altered, exercising mice also showed reduced anxiety compared to sedentary control mice. In situ hybridization analysis showed that BDNF mRNA was increased in specific subfields of hippocampus after wheel running. We chose one paradigm, the FST, in which to investigate a functional role for brain-derived neurotrophic factor (BDNF) in the behavioral response to exercise. We tested mice heterozygous for a deletion of the BDNF gene in the FST after wheel-running. Exercising wild-type mice showed the expected antidepressant-like behavioral response in the FST. but exercise was ineffective in improving FST performance in heterozygous BDNF knockout mice. A possible functional contribution of a BDNF signaling pathway to FST performance in exercising mice was investigated using the specific MEK inhibitor PD184161 to block the MAPK signaling pathway. Subchronic administration of PD184161 to exercising mice blocked the antidepressant-like behavioral response seen in vehicle-treated exercising mice in the FST. In summary, chronic wheel-running exercise in mice results in antidepressant-like behavioral changes that may involve a BDNF related mechanism similar to that hypothesized for antidepressant drug treatment.