外侧隔GABAA 受体在帕金森病模型大鼠焦虑样行为中的作用

doi:10.12092/j.issn.1009-2501.2018.07.003

摘要/Abstract

摘要：

目的: 研究外侧隔（lateral septum, LS）GABA_A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GABAA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, vHip）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vHip 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vHip的5-HT水平及杏仁核和vHip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。

关键词: 外侧隔, GABAA受体, 焦虑, 帕金森病

Abstract:

AIM: To investigate the role of GABA_A receptors 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 (vHip) 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 vHip. However, the doses producing the behavioral effects in the lesioned rats were higher than those in sham-operated rats. CONCLUSION: GABA_A receptors 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 GABA_A receptors.

Key words: lateral septum, GABA_A receptors, anxiety, Parkinson's disease

中图分类号:

R965.2

常永丽，王春雷，原丽，郭晓姝，韩玲娜. 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[J]. 中国临床药理学与治疗学, 2018, 23(7): 734-742.

CHANG Yongli, WANG Chunlei, YUAN Li, GUO Xiaoshu, HAN Lingna. Involvement of lateral septum GABAA receptors in the regulation of anxiety-like behaviors in hemiparkinsonian rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(7): 734-742.

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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 GABAA receptors in the regulation of anxiety-like behaviors in hemiparkinsonian rats

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