Cell Specific Analysis of Psychostimulant Drug Action

描述（由申请人提供）：所有主要滥用药物的作用在很大程度上是通过其增加基底神经节两个部分（丘脑核和背侧纹状体）中多巴胺水平的能力介导的。在这些结构中，增强的多巴胺能神经传递的主要目标是中型多刺神经元。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，不可能对这两种细胞群体分别进行生物化学或转录分析，因为它们在形态上无法区分，在解剖学上相互混合。然而，这两种细胞群之间的差异可能在对滥用药物的反应中很重要。使用一种新的"BAC阵列"方法，mRNA翻译谱将从纹状体和丘脑核的这些细胞中实现。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。将对差异翻译的mRNA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.