氯胺酮对大鼠海马脑片突触长时程增强效应的影响

doi:国家自然科学基金资助课题(30471665)；中国

氯胺酮对大鼠海马脑片突触长时程增强效应的影响

冯春生¹，王金¹，岳云²，麻海春¹，徐海洋¹

1. 吉林大学第一医院麻醉科，吉林长春 130021；2. 首都医科大学附属北京朝阳医院麻醉科，北京 100020

收稿日期:2007-11-13 修回日期:1900-01-01 出版日期:2008-09-28 发布日期:2008-09-28
通讯作者: 徐海洋

Effect of ketamine on synaptic long-term potentiation in hippocampal slices of rats

FENG Chun-sheng¹, WANG Jin¹, YUE Yun², MA Hai-chun¹, XU Hai-yang¹

1. Department of Anesthesiology, First Hospital, Jilin University, Changchun 130021, China; 2. Department of 〖JP2〗Anesthesiology, Beijing Chaoyang Hospital， Affiliated to Capital University of Medical Sciences, Beijing 100020, China

Received:2007-11-13 Revised:1900-01-01 Online:2008-09-28 Published:2008-09-28
Contact: XU Hai-yang

摘要/Abstract

摘要： 目的：观察氯胺酮对大鼠海马脑片突触长时程增强(LTP)效应的影响，并探讨其影响记忆的机制。方法：98只雄性SD大鼠，断头后取出海马组织，制备厚400 μm的海马脑片。取49张脑片，随机分为7组：对照组、氯胺酮1、5、10、30、50和100 μmol•L^-1组。各组脑片分别灌流人工脑脊液(ACSF)、氯胺酮1、5、10、30、50和100 μmol•L^-1。采用细胞外微电极记录技术，记录海马脑片CA1区细胞外群体峰电位(PS)的变化。另取49张脑片，随机分为7组：LTP组、氯胺酮LTP 1、5、10、30、50和100 μmol•L^-1组。各组脑片分别灌流ACSF、氯胺酮1、5、10、30、50和100　μmol•L^-1。海马脑片记录PS 30 min后，施以100 Hz的高频强直刺激(HFS)，诱发LTP，观察各组脑片HFS后PS幅值的变化。结果：与对照组比较，氯胺酮1、5和10 μmol•L^-1组给药后PS幅值无明显改变(P>0.05)，氯胺酮30、50和100 μmol•L^-1组给药后PS幅值明显降低(P<0.01)。LTP组HFS后PS幅值增高，较刺激前增加了(52±12)% (P<0.01)。与LTP组比较，氯胺酮LTP 1和5 μmol•L^-1组HFS后其PS幅值无明显改变(P>0.05)，氯胺酮LTP 10、30、50和100 μmol•L^-1组HFS后其PS幅值均明显降低(P<0.01)。结论：氯胺酮能够抑制海马LTP的形成而影响记忆功能，其机制与抑制海马N-甲基-D-门冬氨酸(NMDA)受体有关。

关键词: 海马, 突触, 长时程增强, 记忆

Abstract: Abstract:Objective To investigate the effect of ketamine on the synaptic long-term potentiation (LTP) in the CA1 area of rat hippocampal slices，and to elucidate the mechanisms underlying the effect of ketamine on memory.Methods Hippocampal slices (400 μm thick) were obtained from the brains of male Sprague-Dawley rats (2 months old) weighing 200-250 g that were decapitated.The slices were incubated in artificial cerebrospinal fluid (ACSF) at room temperature for at least 120 min before use.Forty-nine slices were randomly divided into 7 groups (n=7): control　 group, ketamine 1, 5, 10, 30, 50 and 100 μmol•L^-1 groups.All the slices in each group were perfused with ACSF, ketamine 1, 5, 10, 30, 50 or 100 μmol•L^-1, respectively.The slices in each group were performed to record evoked population spikes (PS) using extracellular microelectrode recording technique.Another forty-nine slices were randomly divided into 7 groups (n=7): LTP group, ketamine-LTP 1, 5, 10, 30, 50 and 100 μmol•L^-1 groups.All the slices in each group were perfused with ACSF, ketamine 1, 5, 10, 30, 50 or 100 μmol•L^-1, respectively.PSs were recorded for at least 30 min before LTP in each group.For LTP induction, high-frequency stimulation (HFS) conditioning pulses (100 Hz•s^-1) were applied to the Schaffer collateral-commissural pathway of hippocampus using a bipolar stimulating electrode.The changes in PS amplitude after HFS were analyzed in each group.Results The PS amplitude of the rat hippocampal slices in ketamine 1, 5, and 10 μmol•L^-1 groups had no significant difference compared with control group.The PS amplitude in ketamine 30, 50 and 100 μmol•L^-1 groups decreased compared with control group (P<0.01).The PS amplitude in group LTP after HFS was significantly increased by (52±12)% compared with pre-HFS, it indicated the successful induction of LTP.The amplitudes of the PS in ketamine-LTP 1 and 5 mol•L^-1 groups did not significantly change after HFS, when compared with LTP group.Compared with LTP group, the amplitudes of the PS in ketamine-LTP 10, 30, 50 and 100 μmol•L^-1 groups after HFS decreased significantly (P<0.01).Conclusion The inhibition of LTP induction in hippocampus of rats may contribute to ketamine-induced deficits in memory, and the underlying mechanism is involved in the inhibition of N-methyl-D-aspartate (NMDA) receptor in hippocampus.

Key words: hippocampus, synapses, long-term potentiation, memory

中图分类号:

R971

冯春生，王金，岳云，麻海春，徐海洋. 氯胺酮对大鼠海马脑片突触长时程增强效应的影响[J]. J4, 2008, 34(5): 746-750.

FENG Chun-sheng, WANG Jin, YUE Yun, MA Hai-chun, XU Hai-yang. Effect of ketamine on synaptic long-term potentiation in hippocampal slices of rats[J]. J4, 2008, 34(5): 746-750.

[1]	王玮瑶, 张岩, 赵可, 孙传博, 金清华. 海马齿状回区多巴胺D1受体在大鼠主动回避学习中的作用及其机制[J]. 吉林大学学报(医学版), 2018, 44(06): 1138-1143.
[2]	王天月, 崔晓燕, 吴骁, 王丹. 磷酸化胞外信号调节激酶在小鼠海马发育过程中的表达及其意义[J]. 吉林大学学报(医学版), 2018, 44(05): 979-982.
[3]	王玮瑶, 陈玲, 岳学玲, 金清华. 慢性束缚应激对老龄大鼠空间学习和记忆能力及海马齿状回区兴奋性氨基酸水平的影响[J]. 吉林大学学报(医学版), 2018, 44(01): 8-12.
[4]	毛西京, 王敏, 于挺敏, 姚刚. 丁苯酞对血管性痴呆大鼠海马CA1区脑源性神经营养因子表达的影响[J]. 吉林大学学报(医学版), 2017, 43(05): 857-861.
[5]	李宁, 刘聪, 李佳鸿, 刘畅, 杨鹏, 王春梅, 敬舒, 孙靖辉, 陈建光, 李贺. 五味子淫羊藿混合提取物对东莨菪碱致小鼠学习记忆障碍的改善作用[J]. 吉林大学学报(医学版), 2017, 43(01): 42-46.
[6]	罗浩铭, 陈英红, 周婷婷, 洪铁, 姜瑞芝, 王颖, 杨晓虹, 马莉. 人参糖蛋白对小鼠学习和记忆能力的影响[J]. 吉林大学学报(医学版), 2016, 42(03): 439-445.
[7]	万朋, 高俊涛, 王丹, 王师, 金清华. 血管性痴呆大鼠海马齿状回区D1受体的表达[J]. 吉林大学学报(医学版), 2015, 41(06): 1130-1133.
[8]	田晶, 邹荣军, 梁祖凤, 石婉婷, 齐玲, 李妍. 尼氟灭酸对氯化钴诱导海马神经元凋亡的抑制作用[J]. 吉林大学学报(医学版), 2015, 41(05): 914-918.
[9]	李雷, 王永杰, 陈浩, 秦永刚, 周煜博, 赵嘉勋, 郭丽. 严重烧伤对大鼠海马神经细胞自噬和神经胶质细胞反应的诱导作用[J]. 吉林大学学报(医学版), 2015, 41(05): 898-901.
[10]	隋竹欣, 李珍, 刘昊, 袁杨, 王海涛. p-Tau蛋白在抑郁症大鼠海马组织中的表达[J]. 吉林大学学报(医学版), 2015, 41(02): 245-248.
[11]	杨振军,赵亮,薛景凤. 慢性脑缺血对大鼠海马微血管构筑及胆碱乙酰基转移酶蛋白表达的影响[J]. 吉林大学学报(医学版), 2014, 40(06): 1216-.
[12]	徐爱军，刘昊，田艳霞，赵毓芳，阚泉，陈志新，王海涛. 柴胡疏肝散对抑郁症大鼠行为学和海马神经元凋亡及自噬的影响[J]. 吉林大学学报(医学版), 2014, 40(04): 801-804.
[13]	王祥，宋军学，张文嘉，赵航，郑杨，李幼琼. 健康人群海马与侧脑室颞角的磁共振线性测量及其意义[J]. 吉林大学学报(医学版), 2014, 40(01): 178-182.
[14]	孙艺学，王爱兵，车冠宇，李子义，张学明. 人α-突触核蛋白A30P突变对小鼠嗅球神经发生的影响[J]. 吉林大学学报(医学版), 2014, 40(01): 74-77.
[15]	李玲玲,孙艺学,王爱兵,李子义,张学明. 人α-突触核蛋白A30P突变对小鼠成体大脑吻端迁移流中神经发生的抑制作用及其机制[J]. 吉林大学学报(医学版), 2013, 39(6): 1186-1189.