Ethanol's effects on the central nervous system (CNS) are mediated by genes and gene products expressed in a variety of regions and specific neuron types. Administration of ethanol changes the expression of specific genes dependent on dose and duration of exposure, and the particular tissue and cell type. These changes can be different or opposite in specific cell types, or may occur in only particular cell types, and may be relatively large or very subtle. Furthermore, it is clear that the response to ethanol is not confined to one or a few genes, but rather is a complex, dynamical process involving the coordinate regulation of large numbers of genes over time. Due to very rapid progress in genomic sequencing and in methods of large-scale high-throughout gene expression analysis, it is now possible to determine the response of genes on a large scale, making it possible in principle to discover the gene networks and cellular controls of alcohol effects on the brain. We propose to do this by focusing on four specific aims: (1) Identify which genes are expressed in specific neuron types and brain regions classically associated with the brain's physiological response to ethanol, including entral mesencephalic dopamine neurons and their forebrain targets and brainstem norepinephrine neurons and their limbic targets. (2) Determine which of the genes expressed in the above neuron types mediate the effects of ethanol, both in alcohol exposure and withdrawal. (3) Create an """"""""Alcohol Stress Chip"""""""" containing both control and experimentally determined sets of genes associated with ethanol's effects on the CNS by 1a and 1b results. (4) Make the results useful to the wider research and NIAAA community.
