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开心散对慢性应激抑郁模型大鼠学习记忆的影响
引用本文:刘明,闫娟娟,周小江,胡园,刘屏. 开心散对慢性应激抑郁模型大鼠学习记忆的影响[J]. 中国中药杂志, 2012, 37(16): 2439-2443
作者姓名:刘明  闫娟娟  周小江  胡园  刘屏
作者单位:1. 解放军总医院临床药理研究室,北京100853;天津中医药大学,天津300193
2. 解放军总医院临床药理研究室,北京,100853
基金项目:国家 重大新药创制科技重大专项(2008ZXJ09004-028)
摘    要:目的:研究经典古方开心散对慢性应激抑郁模型(CMS)大鼠学习记忆能力的影响及可能的作用机制。方法:将大鼠随机分为正常组、模型组、阳性药物组(盐酸氟西汀10 mg.kg-1)、开心散各剂量组(1 000,500,250,125 mg.kg-1),建立CMS大鼠模型,连续灌胃21 d;采用糖水消耗试验、旷场试验评价开心散抗抑郁行为学活性,采用Morris水迷宫评价开心散对CMS大鼠学习记忆能力的影响,并测定各组大鼠全脑中单胺类递质、乙酰胆碱(Ach)和乙酰胆碱酯酶(AchE)活性和海马中脑源性神经营养因子(BDNF)蛋白水平。结果:行为学测试结果表明开心散能明显提高CMS大鼠的糖水偏嗜度和旷场试验总路程,明显缩短Morris水迷宫定位导航的潜伏期,增加空间探索中的穿越平台次数、原平台所在象限游泳距离和时间;增加动物全脑中5-羟色胺(5-HT)、多巴胺(DA)、去甲肾上腺素(NE)和Ach的含量,并提高海马内BDNF的水平,减少AchE。结论:开心散可明显改善CMS大鼠的抑郁行为,增强CMS大鼠学习记忆的能力,其作用的机制可能与增加全脑中单胺递质和Ach含量,提高海马神经营养能力有关。

关 键 词:慢性应激抑郁模型  Morris水迷宫  学习记忆  开心散
收稿时间:2011-08-26

Effect of Kaixin San on learning and memory in chronic stress depression model rats
LIU Ming,YAN Juanjuan,ZHOU Xiaojiang,HU Yuan and LIU Ping. Effect of Kaixin San on learning and memory in chronic stress depression model rats[J]. China Journal of Chinese Materia Medica, 2012, 37(16): 2439-2443
Authors:LIU Ming  YAN Juanjuan  ZHOU Xiaojiang  HU Yuan  LIU Ping
Affiliation:Department of Clinical Pharmacology, Center of Pharmacy, Chinese PLA General Hospital, Beijing 100853, China;Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China;Department of Clinical Pharmacology, Center of Pharmacy, Chinese PLA General Hospital, Beijing 100853, China;Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China;Department of Clinical Pharmacology, Center of Pharmacy, Chinese PLA General Hospital, Beijing 100853, China;Department of Clinical Pharmacology, Center of Pharmacy, Chinese PLA General Hospital, Beijing 100853, China;Department of Clinical Pharmacology, Center of Pharmacy, Chinese PLA General Hospital, Beijing 100853, China
Abstract:Objective : To study the effect of classic ancient prescription Kaixin San (KXS) on learning and memory abilities in chronic stress depression model rats and its possible mechanisms. Method : Rats were randomly assigned to six groups: the control group, the model group, the positive drug group (fluoxetine 10 mg·kg-1) and KXS groups (1 000, 500, 250, 125 mg·kg-1). KXS were orally administrated to CMS rats for 21 days. The anti-depression activity of KXS was assessed using the sucrose consumption and the open-field test. The protecting effect for learning and memory abilities was assessed using the Morris water maze (MWM) test. Furthermore, the levels of monoamine neurotransmitters, acetylcholine (Ach) and acetyl cholinesterase (AchE) in the total brain and brain-derived neurotrophic factor (BDNF) protein in the hippocampus were determined. Result : The behavior test showed that KXS significantly increased the sucrose consumption and total distance in the open-field test and notably reduce the incubation period of location and navigation in the MWM test. It could also help increase the number of times passing through the platform, the swimming distance and time in quadrant of original platform, the levels of serotonin (5-HT) and dopamine (DA), noradrenergic (NE), Ach, BDNF protein and reduce the level of AchE in the CMS-induced rats. Conclusion : KXS can ameliorate the CMS-induced depression behavior in rats and improved their learning and memory abilities, which may be related to the increase in monoamine neurotransmitters, Ach and BDNF levels.
Keywords:chronic stress depression model  Morris water maze  learning and memory  Kaixin San
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