Chronic stress induces anxiety disorders, whereas physical exercise is believed to help people with clinical anxiety. In the present study, we investigated the mechanisms underlying stress-induced anxiety and its counteraction by exercise using an established animal model of anxiety. Mice treated with restraint for 2 h daily for 14 days exhibited anxiety-like behaviors, including social and nonsocial behavioral symptoms, and these behavioral impairments lasted for more than 12 weeks after the stress treatment was removed. Despite these lasting behavioral changes, wheel-running exercise treatment for 1 h daily from post-stress days 1 - 21 counteracted anxiety-like behaviors, and these anxiolytic effects of exercise persisted for more than 2 months, suggesting that anxiolytic effects of exercise stably induced. Repeated restraint treatment up-regulated the expression of the neuropeptide, melanin-concentrating hormone (MCH), in the lateral hypothalamus, hippocampus, and basolateral amygdala, the brain regions important for emotional behaviors. In an in vitro study, treatment of HT22 hippocampal cells with glucocorticoid increased MCH expression, suggesting that MCH upregulation can be initially triggered by the stress hormone, corticosterone. In contrast, post-stress treatment with wheel-running exercise reduced the stress-induced increase in MCH expression to control levels in the lateral hypothalamus, hippocampus and basolateral amygdala. Administration of an MCH receptor antagonist (SNAP94847) to stress-treated mice was therapeutic against stress-induced anxiety-like behaviors. These results suggest that repeated stress produces long-lasting anxiety-like behaviors and upregulates MCH in the brain, while exercise counteracts stress-induced MCH expression and persisting anxiety-like behaviors.

中文翻译：

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体育锻炼可以抵消压力诱导的大脑中黑色素浓缩激素的上调和压力诱导的持续性焦虑样行为。

慢性压力会诱发焦虑症，而体育锻炼被认为可以帮助患有临床焦虑症的人。在本研究中，我们使用已建立的动物焦虑模型，研究了压力诱发的焦虑及其通过运动引起的反作用的机制。每天用约束力治疗的小鼠连续2天每天2 h表现出焦虑样行为，包括社交和非社交行为症状，这些应激障碍在消除压力治疗后持续了超过12周。尽管行为发生了这些持久的变化，但从应激后的1-21天开始每天进行1小时的滚轮运动治疗可以抵消类似焦虑的行为，并且这些运动的抗焦虑作用持续了超过2个月，这表明运动的抗焦虑作用稳定地产生了。反复的约束治疗上调了下丘脑外侧，海马和基底外侧杏仁核中神经肽，黑色素浓缩激素（MCH）的表达，而大脑下部对情感行为至关重要。在一项体外研究中，用糖皮质激素治疗HT22海马细胞会增加MCH表达，这表明MCH上调最初可能是由应激激素皮质酮触发的。相比之下，轮转锻炼的压力后治疗减少了压力诱导的MCH表达增加，从而控制了下丘脑外侧，海马和基底外侧杏仁核的水平。向应激治疗的小鼠施用MCH受体拮抗剂（SNAP94847）可对抗应激引起的焦虑样行为。