大鼠双侧腹侧被盖区头端毁损与抑郁行为的相关性  

Correlation between bilateral lesion of anterior ventral tegmental area and depression-like behavior in rats

作　　者：刘盼 吴仲恒[1] 李立博[1] 乔鸿飞[1] 袁海峰[1] 杜成学 张巧俊[1] LIU Pan;WU Zhong-heng;LI Li-bo;QIAO Hong-fei;YUAN Hai-feng;DU Cheng-xue;ZHANG Qiao-jun(Department of Rehabilitative Medicine,The Second Affiliated Hospital of Xi'an Jiaotong University Health Science Center,Xi'an 710004,China)

机构地区：[1]西安交通大学第二附属医院康复医学科

出　　处：《西安交通大学学报（医学版）》2019年第4期564-568,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省社会发展科技攻关项目(No.2016SF-056);国家自然科学基金项目(No.81873783)~~

摘　　要：目的探索大鼠中脑双侧腹侧被盖区头端(anterior ventral tegmental area,aVTA)在抑郁行为发生机制中的作用。方法以6-OHDA损毁aVTA模型大鼠为研究对象,采用行为学方法(旷场实验、强迫游泳实验和蔗糖偏好实验)观察术后大鼠行格数、直立次数、不动时间、蔗糖消耗百分比的变化;以TH阳性神经元计数观察损毁组大鼠双侧aVTA和SNc的DA神经元损毁程度;通过高压液相在线递质测量技术测定大鼠相关脑区DA、5-HT和NA的含量变化,并与假手术组进行比较。结果①损毁组大鼠的穿行格数、直立次数显著降低,不动时间显著延长,蔗糖消耗百分比显著降低,差异均有统计学意义( P 值均<0.001);②损毁组大鼠aVTA及SNc的DA能神经元数目显著减少( P 值均<0.001 );③损毁组大鼠的内侧前额叶皮质(medial prefrontal cortex,mPFC)、纹状体(striatum,STr)、腹侧海马(ventral hippocampus,VHPC)、外侧缰核(lateral habenula,LHb)中5-HT和NA的含量明显下降( P <0.001);STr中DA含量明显下降( P <0.001),而mPFC、LHb、VHPC中的DA含量变化没有统计学差异( P >0.05)。结论大鼠腹侧被盖区头端参与抑郁行为的发生,腹侧被盖区及其相关脑区单胺类神经递质的改变可能是其原因。Objective To explore the correlation between bilateral anterior ventral tegmental area(aVTA) and depression-like behavior in rats. Methods The subjects in the study were aVTA-lesioned rats which were prepared by microinjecting 6-OHDA into their aVTA nucleus. Four weeks after the operation, all the rats were examined by behavior tests, including open-field test, sucrose preference test, and forced swimming test. We recorded and calculated the number of squares crossed, rearings, sucrose preference, immobility time. Immunohistochemistry method was used to observe the change of TH-positive neurons’ number in bilateral aVTA and SNc of the 6-OHDA lesioned rats. Meanwhile, we analyzed and compared the changes of DA, 5-HT, NE levels in themPFC, LHb, STr and VHPC in the two groups of rats by high performance liquid chromatography with electrochemical detection(HPLC-ED). Results ① Bilateral aVTA lesions in the rats significantly decreased the number of squares crossed and rearings and sucrose preference, increased immobility time when compared with the sham-operated rats(P<0.001). ② In the lesioned rats, the aVTA of the bilateral injected side showed partial loss of TH-ir neurons when compared with the sham-operated rats, and the bilateral SNc in aVTA lesioned rats had a coherence of changing trend, showed a certain decrease(P<0.001). ③ Compared with sham-operated rats, bilateral aVTA 6-OHDA lesioned rats’ 5-HT levels in the mPFC, STr, LHB and VHPC significantly decreased. Likewise, 6-OHDA lesioned rats’ NA levels in the mPFC, striatum, and habenula vHPC significantly decreased, too (P<0.001).However,bilateral aVTA6-OHDA lesioned rats'DA levels only in the striatum showed significantly decreased when compared to the sham-operated rats(P<0.001).Conclusion Bilateral aVTA is involved in depression-like behavior.DA neurons of the VTA and the changes of monoamine neurotransmitters of the limbic and limbic-related areas may be involved in the development of depression.

关 键 词：腹侧被盖区头端 行为学 抑郁 神经递质 

分 类 号：R338.2[医药卫生—人体生理学]