잠시만 기다려 주세요. 로딩중입니다.

Intranasal Administration of Melanin-Concentrating Hormone Reduces Stress-Induced Anxiety- and Depressive-Like Behaviors in Rodents

Experimental Neurobiology 2020년 29권 6호 p.453 ~ 469
소속 상세정보

Abstract


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.

키워드

Depression; Mammalian target of rapamycin (mTOR); Melanin-concentrating hormone (MCH); Stress; Anxiety; Rapamycin

원문 및 링크아웃 정보

등재저널 정보