Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Department of Neurology, Huainan First Peoples' Hospital, Huainan, Anhui, 232007, China.
Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China.
Behav Brain Res. 2019 May 17;364:75-84. doi: 10.1016/j.bbr.2019.01.057. Epub 2019 Feb 10.
Chronic stress is an important factor for depression. Most individuals recover from stress, while some develop into depression. The pathogenesis of resilience or susceptibility remains unclear. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis and releases stress hormones to regulate individual response to stress. Hence, we assessed the effects of chronic social defeat stress (CSDS) on susceptible behaviors, plasma corticosterone (CORT) concentration, glucocorticoid receptor (GR) expressions in hippocampus and medial prefrontal cortex (mPFC). Mice that plasma CORT concentration is increased 2 h after single social defeat stress developed into susceptible mice after 10 d social defeat stress. The plasma CORT concentration was still higher than that of resilient mice 48 h after the last defeat stress. Mice administered CORT via drinking water showed susceptibility. Mifepristone, a GR antagonist improved susceptibility to chronic stress. Single dose ketamine treatment improved depressive-like behaviors, decreased plasma CORT concentration, rescued GR expression and nuclear translocation in the hippocampus of susceptible mice. These results suggested that abnormal CORT concentration after stress may predict susceptibility to depression in clinic. Ketamine may exert the antidepressant effect via normalizing HPA axis response and have significance in the clinic.
慢性应激是抑郁的一个重要因素。大多数人从压力中恢复过来，而有些人则发展成抑郁。韧性或易感性的发病机制仍不清楚。应激激活下丘脑-垂体-肾上腺（HPA）轴并释放应激激素，以调节个体对压力的反应。因此，我们评估了慢性社会挫败应激（CSDS）对易感行为、血浆皮质酮（CORT）浓度、海马和内侧前额叶皮质（mPFC）中糖皮质激素受体（GR）表达的影响。在单次社会挫败应激后 2 小时血浆 CORT 浓度升高的小鼠，在 10 天的社会挫败应激后发展为易感小鼠。最后一次挫败应激后 48 小时，血浆 CORT 浓度仍高于应激抵抗小鼠。通过饮用水给予 CORT 的小鼠表现出易感性。GR 拮抗剂米非司酮改善了对慢性应激的易感性。单次氯胺酮治疗可改善抑郁样行为，降低易感小鼠血浆 CORT 浓度，挽救海马 GR 表达和核易位。这些结果表明，应激后异常的 CORT 浓度可能预示着临床抑郁的易感性。氯胺酮可能通过使 HPA 轴反应正常化发挥抗抑郁作用，在临床上具有重要意义。
