Cell Specific Analysis of Psychostimulant Drug Action

描述(由申请人提供)：所有主要药物滥用的影响在很大程度上是通过它们提高基底神经节两个部分-伏隔核和背侧纹状体-多巴胺水平的能力来调节的。在这些结构中，多巴胺能神经传递增强的主要靶点是中棘神经元。这些神经元主要有两类：直接通路细胞和间接通路细胞，这是一种基于轴突投射靶点的分类。到目前为止，还不可能对这两个细胞群体分别进行生化或转录分析，因为它们在形态上难以区分，在解剖学上相互混合。然而，这两个细胞群之间的差异在应对药物滥用方面可能很重要。使用一种新的‘BACarray’方法，将从纹状体和伏隔核的这些细胞中获得mRNA的翻译图谱。在初步确定了两种细胞群之间的差异后，将确定急性和慢性精神刺激剂给药对每种细胞类型翻译的mRNAs谱的影响。将对差异翻译的mRNAs对滥用药物的细胞反应的影响进行初步表征。

DESCRIPTION (provided by applicant): The effects of all major drugs of abuse are mediated in large part by their ability to increase levels of dopamine in two parts of the basal ganglia, the nucleus accumbens and dorsal striatum. In these structures, the major targets of enhanced dopaminergic neurotransmission are medium-spiny neurons. Two major classes of these neurons exist: direct and indirect pathway cells, a classification based on the target site of axonal projection. Until now it has been impossible to perform biochemical or transcriptional profiling on these two cell populations separately because they are morphologically indistinguishable and anatomically intermixed. However, differences between these two cell populations are likely to be important in the response to drugs of abuse. Using a novel 'BACarray' methodology, mRNA translational profiling will be achieved from these cells of the striatum and nucleus accumbens. After an initial characterization of differences between the two cell populations, the effects of acute and chronic psychostimulant administration on the profile of mRNAs translated in each cell type will be determined. A preliminary characterization of the effects of differentially translated mRNAs on the cellular response to drugs of abuse will be conducted.