Li Jing, Sun Jian-Dong, Liu Yan, Yuan Yu-He, Chen Nai-Hong
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Yao Xue Xue Bao. 2013 Aug;48(8):1221-6.
This study is to investigate the amelioration effect of glucocorticoid receptor (GR) antagonist mifepristone on the changes of learning and memory abilities in rat model of depression. In the present study, a 35-day rat chronic unpredictable stress (CUS) model was used to observe both depression-like behaviors with sucrose preference test and open-field test and learning and memory-associated behaviors with Morris water maze test. A total of 45 male adult Sprague-Dawley rats were randomly assigned to three groups of equal size: control group (CON); CUS group (CUS); CUS + mifepristone group (CM). Animals in CM group were first exposed to CUS for 14 days, and then were administered with 50 mg x kg(-1) x d(-1) of mifepristone with continued CUS procedure. Corticosterone EIA Kit was used to detect the concentration of plasma corticosterone (CORT). Nissl staining was used to observe the structure of hippocampus. The results demonstrated that CUS exposure induced both depressive-like and learning and memory-associated behaviors and these deficits were reversed by mifepristone. Compared to CON group, the concentration of plasma CORT increased significantly in CUS group. CUS exposure damaged the structure of hippocampus, whereas mifepristone had an amelioration effect. Together, the structural deficits of hippocampus resulting from long-term stress exposure, which could contribute to the impairment of learning and memory in depression, are reversed by the GR receptor antagonist mifepristone.
本研究旨在探讨糖皮质激素受体(GR)拮抗剂米非司酮对抑郁症大鼠模型学习记忆能力变化的改善作用。在本研究中,采用35天的大鼠慢性不可预测应激(CUS)模型,通过蔗糖偏好试验和旷场试验观察抑郁样行为,通过莫里斯水迷宫试验观察学习记忆相关行为。将45只成年雄性Sprague-Dawley大鼠随机分为三组,每组数量相等:对照组(CON);CUS组(CUS);CUS + 米非司酮组(CM)。CM组动物先接受14天的CUS处理,然后给予50 mg·kg⁻¹·d⁻¹的米非司酮并继续CUS处理。使用皮质酮酶联免疫吸附测定试剂盒检测血浆皮质酮(CORT)浓度。采用尼氏染色观察海马结构。结果表明,CUS暴露诱导了抑郁样行为以及学习记忆相关行为,而这些缺陷被米非司酮逆转。与CON组相比,CUS组血浆CORT浓度显著升高。CUS暴露损害了海马结构,而米非司酮具有改善作用。总之,长期应激暴露导致的海马结构缺陷可导致抑郁症患者学习记忆受损,而GR受体拮抗剂米非司酮可逆转这一缺陷。