Chronic multiple mild stress induces sustained adverse psychological states in rats

压力源 不利影响 前额叶皮质 舍曲林 帕罗西汀 海马体 心理学 内分泌学 内科学 无血性 糖皮质激素 氟西汀 神经营养因子 糖皮质激素受体 促肾上腺皮质激素释放激素 社会失败 抗抑郁药 医学 神经科学 激素 受体 血清素 认知 多巴胺
作者
Tianze Yu,Yi Chen,Jiani Lu,Luyun Gong,Yuechen Mao,Xinya Liu,Yiying Zhou,Lei Guo,Xiang Wu,Junfang Zhang,Chuang Wang,Haowei Shen,Wenhua Zhou,Disen Mei,Wei Cui
出处
期刊:Neuroreport [Ovid Technologies (Wolters Kluwer)]
卷期号:33 (15): 669-680
标识
DOI:10.1097/wnr.0000000000001832
摘要

Adverse psychological states are stimulated by multiple types of environmental factors in human being. However, only few animal models of adverse psychological states were established by applying multiple types of stressors to mimic real conditions. A multisensory stress simulation device was designed to apply a combination of stressors to animals. Selected types and intensity of stressors were stimulated by this multisensory stress simulation device to induce chronic multiple mild stress (CMMS) in rats, modeling sustained adverse psychological states caused by long-term exposure in relative extreme environments with limited social interaction in human being. Fourteen-day treatment of CMMS-induced anhedonia, anxiety, and the loss of body weight in rats, which were similar to those in human being with adverse psychological states. Moreover, CMMS treatment leads to decreased production of serotonin and increased expression of corticotropin-releasing factor receptor 1, adrenocorticotropic hormone, and glucocorticoid in the brain, which were prevented by paroxetine and sertraline, two clinical-used antidepressants. Furthermore, these antidepressants prevented the CMMS-induced inhibition of brain-derived neurotrophic factor/cAMP-response element binding protein pathway, reduction of synaptic protein expression, and the activation of microglia and astrocytes in the hippocampus and the prefrontal cortex of rats. In addition, 14-day CMMS-induced long-term depressive-like behaviors, even after 14 days of CMMS treatment. And sertraline reversed CMMS-induced behavioral and biochemical changes in rats. All these results suggested that CMMS protocol induced sustained adverse psychological states in rats. By adjusting the intensity and the type of stressors in the multisensory stress simulation device, it might be practicable to establish animal models with complicated and changeable environmental factors.

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