外侧缰核中5-HT_(2C)受体在帕金森病模型大鼠焦虑行为中的调节作用及其机制  

Regulatory effects of 5-HT_(2C) receptors in lateral habenular nucleus on anxiety behaviors in rat models of Parkinson's disease and their mechanisms

作　　者：韩玲娜[1] 王春雷[2] 张莉[3] 

机构地区：[1]长治医学院生理学教研室,山西长治046000 [2]长治医学院生物医学工程系,山西长治046000 [3]西安交通大学医学部生理学与病理生理学系,陕西西安710061

出　　处：《吉林大学学报（医学版）》2016年第3期473-480,共8页Journal of Jilin University：Medicine Edition

基　　金：陕西省科技厅国际合作与交流计划项目资助课题(2015KW-040);长治医学院科技创新团队项目资助课题(CX201506)

摘　　要：目的:探讨外侧缰核(LHb)中5-羟色胺2C(5-HT_(2C))受体在调节帕金森病(PD)大鼠相关焦虑行为中的作用,阐明PD相关焦虑行为的神经机制。方法:将126只大鼠随机分为假手术组(n=63)和黑质致密部(SNc)损毁组(n=63)。采用行为学方法观察2组大鼠在旷场实验中的中央区停留时间百分比、高架十字迷宫实验(EPM)中的开放臂进入次数百分比和开放臂停留时间百分比;采用高效液相色谱-电化学检测法观察大鼠边缘相关脑区中单胺类递质水平;采用组织学和免疫组织化学染色法确认套管位置及SNc损毁后多巴胺(DA)神经元的缺失程度。结果:与假手术组比较,SNc损毁组大鼠中央区停留时间百分比(F1,72=36.678,P<0.001)、开放臂进入次数百分比(F1,72=59.077,P<0.001)和开放臂停留时间百分比(F1,72=84.245,P<0.001)均明显降低,且内侧前额叶皮层(mPFC)(P<0.01)、杏仁核(P<0.01)和海马(P<0.05)中DA水平均明显下降;LHb中局部注射5-HT_(2C)受体激动剂Ro60-0175后,与未加入Ro60-0175时比较,2组大鼠中央区停留时间百分比(P<0.05或P<0.01)、开放臂进入次数百分比(P<0.05或P<0.01)和开放臂停留时间百分比(P<0.05或P<0.01)均明显降低;且mPFC、杏仁核和海马中3种单胺类递质DA、5-HT和去甲肾上腺素(NA)水平均不同程度下降。在mPFC,2组大鼠给予Ro60-0175后,3种递质水平均明显降低(P<0.05或P<0.01);在杏仁核,给予Ro60-0175后,除5-HT水平无明显变化外,其余2种递质水平明显下降(P<0.05或P<0.01);在海马,给予Ro60-0175后,除假手术组大鼠NA水平无变化外,其余均明显下降(P<0.05或P<0.01)。组织学确认行为学实验中使用大鼠套管均位于LHb上方1mm;免疫组织化学检测,SNc损毁组大鼠损毁侧SNc中DA神经元完全缺失,且腹侧被盖区DA神经元较未损毁侧明显减少(P<0.001)。结论:LHb中5-HT_(2C)受体的激活可诱发或增强大鼠的焦虑行为,其机制与相关脑区中单胺类递质水平变化有关联。Objective：To study the effects of 5-hydroxytryptamine 2C（5-HT（2C））receptors in the lateral habenular nucleus（LHb）on anxiety behaviors in the rats with Parkinson＇s disease（PD）,and to clarify the neural mechanisms of PD associated anxiety behaviors.Methods：A total of 126 rats were randomly divided into sham operation group（n =63）and substantia nigrapar compacta（SNc）lesion group（n=63）.The anxiety behaviors of rats in two groups such as the percentages of the time spending in center region were observed by the open field test,and the percentages of number of open arm entries and time of open arm staying were observed by elevated plus maze test;the monoamine levels in limbic related brain regions were assessed by high performance liquid chromatography with electrochemical detection;the cannula position and the degeneration of dopamine（DA）neurons after SNc lesion were confirmed by histological and immunohistochemical staining.Results：Compared with sham operation group,the percentage of time spending in center region（F1,72= 36.678,P〈0.001）,the percentage of number of open arm entries（F1,72= 59.077,P〈0.001）and the percentage of time of open arm staying（F1,72= 84.245,P〈0.001）of the rats in SNc lesion group were decreased.The DA levels in medial prefrontal cortex（mPFC）（P〈0.01）,amygdala（P〈0.01）,and hippocampus（P〈0.05）of the rats in SNc lesion group were significantly decreased compared with sham operation group.Compared with the rats treated with vehicle in the same group,the intra-injection of 5-HT2 Creceptors agonist Ro60-0175 could significantly decrease the percentages of time spending in center region（P〈0.01 or P〈0.01）,the percentages of number of open arm entries（P〈0.05 or P〈0.01）,and the percentages of time of open staying（P〈0.05 or P〈0.01）and the monoamine levels in mPFC,amygdala and hippocampus of the rats.Three monoamine levels in mPFC of the rats in two groups were decreased significantly（P〈0.05 or P〈0.01

关 键 词：帕金森病 焦虑 外侧缰核 5-HT(2C)受体 

分 类 号：R338.8[医药卫生—人体生理学] R742[医药卫生—基础医学]