Cell Specific Analysis of Psychostimulant Drug Action

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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.