米非司酮对抑郁模型大鼠学习记忆能力的干预作用  

Mifepristone repairs alteration of learning and memory abilities in rat model of depression

作　　者：李婧[2] 孙建栋 刘岩 苑玉和 陈乃宏 

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,新药作用机制研究与药效评价北京市重点实验室,北京100050 [2]天津中医药大学,天津300193

出　　处：《药学学报》2013年第8期1221-1226,共6页Acta Pharmaceutica Sinica

基　　金：国家高技术研究发展计划(863计划)资助项目(2012AA020303);长江学者和创新团队发展计划资助项目(PCSIRT NO.IRT1007);国家自然科学基金资助项目(81274122,81102831,81173578,81273629,81001487);国家国际科技合作项目(2010DFB32900);创新药物研究开发技术平台建设资助项目(2012ZX09301002-004,2012ZX09103101-006);教育部博士点基金重点项目(20121106130001);北京市自然科学基金重点项目(7131013);北京市重点实验室基金资助项目(BZ0150)

摘　　要：观察抑郁症模型大鼠学习记忆能力的改变及糖皮质激素受体拮抗剂米非司酮的干预作用。取雄性Sprague-Dawley大鼠,随机分为正常对照组(CON组)、慢性不可预知性应激组(chronic unpredictable stress,CUS组)和米非司酮组(CM组)。后两组采用35天慢性不可预知性应激建立抑郁症模型,建模14天起CM组给予米非司酮50 mg.kg 1.d 1。采用旷场实验、糖水消耗量实验及Morris水迷宫实验测试大鼠的行为学改变;CorticosteroneEIA Kit测定大鼠血浆皮质酮(corticosterone,CORT)含量;尼氏染色检测大鼠海马的形态学变化。结果表明,与CON组相比,CUS组大鼠行为学测试显示其直立活动及水平活动减少、糖水摄入百分比减少及学习记忆力下降;血浆中皮质酮含量明显升高;尼氏染色显示,CUS组大鼠海马CA3区细胞层变薄,细胞间隙增大,排列紊乱疏松,而CM组在上述行为学和海马形态方面有明显的改善。结果提示,CUS可导致大鼠产生抑郁症状和学习记忆功能障碍,米非司酮对其有改善作用,该现象可能与应激导致大鼠下丘脑垂体肾上腺轴功能亢进、血浆中CORT水平增加引起海马结构损伤有关。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·kg^-1·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.

关 键 词：米非司酮 慢性不可预知性应激 学习记忆 抑郁症 皮质酮 海马 

分 类 号：R965[医药卫生—药理学]