Partial, graded losses of dopamine terminals in the rat caudate-putamen: an animal model for the study of compensatory adaptation in preclinical parkinsonism
Partial, graded losses of dopamine terminals in the rat caudate-putamen: an animal model for the study of compensatory adaptation in preclinical parkinsonism
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DOI：
10.1016/s0165-0270(00)00372-1
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发表时间：
2001-03-30
影响因子：
3
通讯作者：
Garris, PA
中科院分区：
文献类型：
--
作者：
Bergstrom, BP;Schertz, KE;Garris, PA
本研究以部分、分级的方式损毁支配大鼠尾壳核（CP）的多巴胺（DA）神经元。我们的目标是提供一个病变模型，支持动物内比较伏安记录用于调查DA神经传递的补偿适应。病变利用的地形学中纹状体DA神经元，神经毒素6-羟基多巴胺（6-OHDA）的内侧和外侧边缘的腹侧中脑含有DA细胞体和显微解剖的CP成6个区域的显微注射。通过HPLC-EC对这些区域中的组织DA含量的分析表明，6-OHDA注射到外侧黑质中导致CP的外侧区域与内侧区域中的DA损失显著更大。通过向内侧SN附近的腹侧被盖区注射6-OHDA，逆转DA分级损失的方向（即内侧至外侧病变梯度）。电诱发DA的细胞外浓度可以测量跨中外侧轴的CP在一个单一的动物使用在体内伏安法的技术。更重要的是，诱发DA水平的幅度的梯度下降一般遵循的方向在病变动物的组织DA梯度。这些结果表明，DA终端在CP的梯度损失，再加上一个空间和时间上解决的技术，用于监测细胞外DA，是一个可行的工具，调查中纹状体DA系统的补偿适应。(C)2001 Elsevier Science B. V.保留所有权利。
Procedures to lesion dopamine (DA) neurons innervating the rat caudate-putamen (CP) in a partial, graded fashion are described in this study. The goal is to provide a lesion model that supports intra-animal comparisons of voltammetric recordings used to investigate compensatory adaptation of DA neurotransmission. Lesions exploited the topography of mesostriatal DA neurons, microinjections of the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial and lateral edges of the ventral mesencephalon containing DA cell bodies and microdissection of the CP into six regions. Analysis of tissue DA content in these regions by HPLC-EC demonstrated that 6-OHDA injected into the lateral substantia nigra results in a significantly greater loss of DA in lateral versus medial regions of the CP. The direction of the graded loss of DA was reversed (i.e. a medial to lateral lesion gradient) by the injection of 6-OHDA into the ventral tegmental area near the medial SN. Extracellular concentrations of electrically evoked DA could be measured across the mediolateral axis of the CP in a single animal using the technique of in vivo voltammetry. More importantly, graded decreases in the amplitude of evoked DA levels generally followed the direction of the tissue DA gradient in lesioned animals. These results suggest that the graded loss of DA terminals in the CP, coupled to a spatially and temporally resolved technique for monitoring extracellular DA, is a viable tool for investigating compensatory adaptation in the mesostriatal DA system. (C) 2001 Elsevier Science B.V. All rights reserved.