激活或阻断内侧隔斜角带复合体中5-HT_(1A)受体对帕金森病模型大鼠认知功能的影响  

Effects of activation or blockade of 5-HT_(1A) receptors in the medial septum-diagonal band of Broca complex on cognitive functions in hemiparkinsonian rats

作　　者：李立博[1] 李坤颖[1] 郭方圆[1] 李文娟[1] 席悦[1] 乔鸿飞[1] 杨峰[1] 张巧俊[1] LI Li-bo;LI Kun-ying;GUO Fang-yuan;LI Wen-juan;XI Yue;QIAO Hong-fei;YANG Feng;ZHANG Qiao-jun(Department of Rehabilitation Medicine,the Second Affiliated Hospital of Xi＇an Jiaotong University,Xi＇an 710004,China)

机构地区：[1]西安交通大学医学院第二附属医院康复医学科,陕西西安710004

出　　处：《西安交通大学学报（医学版）》2018年第4期488-493,497,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省自然科学基础研究计划资助项目(No.2016JQ8012);陕西省科技攻关项目(No.2016SF-056)~~

摘　　要：目的探讨内侧隔斜角带复合体(medial septum-diagonal band of Broca complex,MS-DB)中5-HT1A受体在帕金森病(Parkinson's disease,PD)认知功能中的作用及机制。方法以6-羟基多巴胺(6-hydroxydopamine,6-OHDA)损毁单侧内侧前脑束(medial forebrain bundle,MFB)的PD模型大鼠为对象,采用行为学和电生理学方法,观察激活或阻断MS-DB中5-HT1A受体对PD认知功能和海马theta节律的影响。结果 (1)单侧MFB损毁降低了大鼠在T-迷宫实验中的选择正确率,MS-DB局部注射5-HT1A受体激动剂8-OH-DPAT进一步降低模型组大鼠在T-迷宫实验中的选择正确率,而MS-DB局部注射选择性5-HT1A受体拮抗剂WAY100635升高模型组大鼠的选择正确率;(2)单侧MFB损毁使海马theta节律的峰频率降低,MS-DB局部注射8-OH-DPAT抑制海马theta节律,降低theta节律的标准化功率,而MS-DB局部注射WAY100635诱发海马theta节律,并使theta节律的标准化功率升高。结论阻断MS-DB中的5-HT1A受体可改善模型组大鼠的工作记忆,这可能是通过兴奋海马theta节律来实现的。Objective To explore the role and mechanisms of 5-HT1 Areceptors in the medial septum-diagonal band of Broca complex（MS-DB） in hemiparkinsonian rats. Methods Combined behavioral and electrophysiological studies were performed to assess the role of MS-DB5-HT1 A receptors in working memory and hippocampal theta rhythm in rats with 6-hydroxydopamine（6-OHDA）lesions in the medial forebrain bundle（MFB）.Results（1） MFB lesions in the rats decreased choice accuracy in the T-maze rewarded alternation test.Intra-MS-DB injection of 5-HT1 Areceptor agonist 8-OH-DPAT further decreased choice accuracy,while intra-MSDB injection of 5-HT1 A receptor antagonist WAY-100635 increased choice accuracy in the lesioned rats.（2） MFB lesions in the rats decreased peak theta rhythm frequency.Intra-MS-DB injection of 8-OH-DPAT suppressed hippocampal theta rhythm and decreased normalized theta power,while intra-MS-DB injection of WAY-100635 induced theta rhythm and increased normalized theta power.Conclusion Blockade of MS-DB5-HT1 A receptors can recover cognitive dysfunction in Parkinson＇s disease, which may be attributed to the enhancement of hippocampal theta rhythm.

关 键 词：帕金森病 内侧隔斜角带复合体 5-HT1A受体 认知功能 海马(theta节律) 

分 类 号：R741[医药卫生—神经病学与精神病学]