外侧隔GABA_A受体在帕金森病模型大鼠焦虑样行为中的作用  

Involvement of lateral septum GABA_A receptors in the regulation of anxiety-like behaviors in hemiparkinsonian rats

作　　者：常永丽[1] 王春雷[2] 原丽[1] 郭晓姝[1] 韩玲娜[1] CHANG Yongli;WANG Chunlei;YUAN Li;GUO Xiaoshu;HAN Lingna(Department of Physiology;Department of Biomedical Engineering,Changzhi Medical College,Changzhi 046000,Shanxi,China)

机构地区：[1]长治医学院生理教研室,山西长治046000 [2]长治医学院生物医学工程系,山西长治046000

出　　处：《中国临床药理学与治疗学》2018年第7期734-742,共9页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目(81600951)

摘　　要：目的:研究外侧隔(lateral septum,LS)GABAA受体在帕金森病(Parkinson's disease,PD)模型大鼠焦虑样行为中的作用。方法:将167只大鼠随机分为假手术组(n=85)和单侧内侧前脑束(medial forebrain bundle,MFB)损毁组(n=82)。采用旷场试验和高架十字迷宫实验观察LS局部给予不同剂量的GABA_A受体激动剂muscimol或拮抗剂picrotoxin对两组大鼠焦虑样行为的影响;采用高效液相色谱-电化学检测法观察焦虑相关脑区单胺类神经递质含量的变化。结果:与假手术组比较,MFB损毁组大鼠产生焦虑样行为,且LS、杏仁核、腹侧海马(ventral hippocampus,v Hip)中多巴胺(DA)水平均明显下降。与溶媒组相比,LS中局部注射muscimol后,在两组大鼠中分别诱发或加重焦虑样行为,且LS、杏仁核和v Hip DA、5-羟色胺(5-HT)水平均下降;LS中局部注射picrotoxin后,在两组大鼠中均改善焦虑样行为,且LS、杏仁核和v Hip的5-HT水平及杏仁核和v Hip的DA水平升高;所不同的是产生以上行为学改变所需剂量,MFB损毁组均高于假手术组。结论:LS中GABAA受体调节大鼠焦虑样行为,其机制与边缘相关脑区DA和5-HT递质含量变化有关。AIM：To investigate the role of GABAAreceptors in the lateral septum（LS） in the regulation of anxiety-like behaviors in hemiparkinsonian rats.METHODS：A total of 167 rats were randomly divided into sham-operated group（n = 85）and medial forebrain bundle（MFB） lesioned group（n = 82）.The open field and elevated plus maze（EPM） test were performed to study the influence of MFB lesion and intra-LS injection of GABAA agonist muscimol（0.2,0.4 or 0.8 μg/rat） and antagonist picrotoxin（0.1,0.2 or 0.4 μg/rat） on anxiety-like behaviors.Changes of monoamine levels in limbic related brain regions were observed by high performance liquid chromatography with electrochemical detection.RESULTS：Compared with sham-operated group,the MFB lesioned group induced anxiety-like behaviors.The dopamine（DA） levels in LS,amygdala and ventral hippocampus（v Hip） were significantly decreased compared with sham-opreated group.Compared with the rats treated with vehicle in the same group,the intra-injection of muscimol in LS induced or aggravated the anxiety-like behaviors in two groups,and decreased DA and 5-hydroxytryptamine（5-HT） levels in three brain regions.In contrast,the administration of picrotoxin improved anxiety-like behaviors,and increased 5-HT in three brain regions and DA in amygdala and v Hip.However,the doses producing the behavioral effects in the lesioned rats were higher than those in sham-operated rats.CONCLUSION：GABAAreceptors in the LS are involved in the regulation of anxiety-like behaveiors,which is attributable to changes in dopamine,5-HT levels in the limbic-related brain regions after activation and blockade of GABAAreceptors.

关 键 词：外侧隔 GABAA受体 焦虑 帕金森病 

分 类 号：R965.2[医药卫生—药理学]