Cell Specific Analysis of Psychostimulant Drug Action

描述（由申请人提供）：所有主要滥用药物的影响在很大程度上是由它们增加基底神经节，伏隔核和背纹状体两个部分多巴胺水平的能力介导的。在这些结构中，多巴胺能神经传递增强的主要目标是中棘神经元。这些神经元主要分为两类：直接通路细胞和间接通路细胞，这是基于轴突投射的目标部位进行分类的。到目前为止，对这两种细胞群分别进行生化或转录分析是不可能的，因为它们在形态上难以区分，在解剖学上是混合的。然而，这两种细胞群之间的差异可能对药物滥用的反应很重要。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翻译分析。在对两种细胞群之间的差异进行初步表征后，将确定急性和慢性精神兴奋剂给药对每种细胞类型中翻译的mrna谱的影响。初步表征差异翻译mrna对滥用药物的细胞反应的影响将进行。

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.