西酞普兰对慢性应激大鼠行为及脑内ERK1/2磷酸化水平的影响  

Effect of citalopram on behavioral manifestation and the level of brain phosphorylated ERK1/2 in rats under chronic stress

作　　者：乔昱婷[1] 谭庆荣[1] 王百忍[2] 张瑞国[1] 王怀海[1] 段小莉[2] 

机构地区：[1]第四军医大学附属西京医院心身科,西安710032 [2]第四军医大学神经科学研究所

出　　处：《临床精神医学杂志》2007年第3期148-150,217,共4页Journal of Clinical Psychiatry

基　　金：国家自然科学基金资助项目(30670758);全军十一五攻关课题资助项目(06G096)

摘　　要：目的:探讨西酞普兰能否预防或减弱慢性应激的不良反应及其可能的作用机制。方法:对Sprague Dawley大鼠,随机分为正常对照(NC)组,束缚应激(RS)组和西酞普兰预处理(CP)组。RS组大鼠每日束缚6h,连续21d。利用Morris水迷宫观察大鼠的空间记忆能力,运用免疫组织化学方法观察脑内细胞外信号调节激酶(extracellular signal-regulated kinase1/2,ERK1/2)磷酸化(p-ERK1/2)水平的改变。结果:RS组大鼠的Morris水迷宫试验目标象限活动时间和穿越站台次数比NC组大鼠显著减少(P<0.05);CP组大鼠的上述指标较RS组大鼠明显改善(P<0.05)。RS组大鼠的前额皮质、杏仁内侧核以及杏仁皮质后内侧核中p-ERK1/2阳性细胞数均较NC组显著减少(P<0.05);而CP组大鼠以上各脑区中p-ERK1/2阳性细胞数均较RS组明显增多(P<0.05)。结论:慢性束缚应激后大鼠的空间记忆明显受损;应激前和应激期间给予西酞普兰处理,能明显缓解应激对大鼠造成的记忆损伤,增加脑内ERK信号传导通路的活化。Objective：To investigate whether citalopram can prevent/attenuate the malignant consequence induced by chronic stress and its possible mechanism. Method： Sprague-Dawley （SD） rats were randomly divided into three groups,normal control group （NC）, restraint stress group （RS） and citalopram prevention group （CP）. Rats in RS group were treated with restraint stress for 21 days,6 hour a day. Morris water maze was used to examine the special memory capability, and immunohistochemical methods was used to observe the expression of phosphorylated extracellular signal-regulated kinase 1/2 （p-ERK1/2）. Results： Compared with rats in NC group,the active time at target quadrant and the times of traversing stage in Morris water maze test weresignificantly decrease in rats of RS group （ P 〈 0.05）. However, the indexes above in rats of CP group had been improved well compared with that in rats of RS group （P 〈 0.05）.The amount of p-ERK1/2 positive cells in prefrontal cortex, interior amygdaloid nucleus and posteroimemal cortical amygdaloid nucleus in rats of RS group were significantly reduced compared with that in rats of NC group （ P 〈 0.05）, whereas the amount of p-ERK1/2 positive cells in brain regions above in rats of CP group was significantly increased compared with that in rats of RS group （ P 〈 0.05）. Conclusion： Rats suffered chronic restraint stress had a defect in special memory capability. Citalopram treatment, both before and during the stress, can obviously alleviate the memory damage and enhance the brain activity of ERK signaling pathway.

关 键 词：慢性束缚应激 西酞普兰 MORRIS水迷宫 细胞外信号调节激酶 

分 类 号：R749.053[医药卫生—神经病学与精神病学]