Major depressive disorder is a complex neuropsychiatric disorder with few treatment options. Non-targeted antidepressants have low efficacy and can induce series of side effects. While a neuropeptide, melanin-concentrating hormone (MCH), is known to exhibit regulator of affective state, no study to date has assessed the anti-depressive effects of MCH in a stress-induced depression model. This study aimed to evaluate the pharmacological effects of intranasal administration of MCH on depression-related behavior in stressed rats and mice. Using a number of behavioral tests, we found that MCH treatment significantly decreased anxiety- and depressive-like behaviors induced by stress. Notably, the effects of MCH were equivalent to those of fluoxetine. MCH treatment also restored the activity of the mammalian target of rapamycin (mTOR) signaling pathway and normalized the levels of synaptic proteins, including postsynaptic density 95, glutamate receptor 1, and synapsin 1, which were all downregulated by stress. Interestingly, the protective effects of MCH were blocked by the mTOR inhibitor, rapamycin. These results suggest that MCH exhibits antidepressant properties by modulating the mTOR pathway. Altogether, this study provides an insight into the molecular mechanisms involved in the antidepressant-like effects of MCH, thereby paving the way for the future clinical application of MCH.

中文翻译：

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鼻内施用黑色素浓缩激素可减少啮齿动物的应激诱导的焦虑和抑郁样行为。

重度抑郁症是一种复杂的神经精神疾病，几乎没有治疗选择。非靶向抗抑郁药功效低下，并可能诱发一系列副作用。虽然已知一种神经肽黑色素浓缩激素（MCH）表现出情感状态的调节因子，但迄今为止，尚无研究评估MCH在压力诱发的抑郁症模型中的抗抑郁作用。这项研究旨在评估鼻内施用MCH对应激大鼠和小鼠抑郁相关行为的药理作用。使用许多行为测试，我们发现MCH治疗可显着降低压力引起的焦虑和抑郁样行为。值得注意的是，MCH的效果与氟西汀相当。MCH治疗还恢复了雷帕霉素（mTOR）信号转导途径的哺乳动物靶标的活性，并使突触蛋白的水平正常化，包括突触后密度95，谷氨酸受体1和突触蛋白1，这些均受压力下调。有趣的是，mTOR抑制剂雷帕霉素阻断了MCH的保护作用。这些结果表明，MCH通过调节mTOR途径表现出抗抑郁特性。总而言之，这项研究提供了对涉及MCH的抗抑郁样作用的分子机制的见解，从而为MCH的未来临床应用铺平了道路。mTOR抑制剂雷帕霉素阻断了MCH的保护作用。这些结果表明，MCH通过调节mTOR途径表现出抗抑郁特性。总而言之，这项研究提供了对涉及MCH的抗抑郁样作用的分子机制的见解，从而为MCH的未来临床应用铺平了道路。mTOR抑制剂雷帕霉素阻断了MCH的保护作用。这些结果表明，MCH通过调节mTOR途径表现出抗抑郁特性。总而言之，这项研究提供了对涉及MCH的抗抑郁样作用的分子机制的见解，从而为MCH的未来临床应用铺平了道路。