Analyzing gene expression patterns in genetic models of alcoholism may uncover previously unknown susceptibility genes, and point to novel targets for drug development. Here, we compared expression profiles in alcohol-preferring AA rats with the alcohol-avoiding counterpart ANA line, and unselected Wistar rats. Cingulate cortex, Nc. accumbens, amygdala and hippocampus of each line were analyzed using the Afymetrix RN U34 arrays and dChip 1.1 software. Analysis of line-specific expression revealed 48 differentially expressed genes between AA and ANA rats. Elevated hippocampal neuropeptide Y (NPY) was found in ANA rats in agreement with previous studies. A cluster of MAP-kinases indicating altered signal transduction was upregulated within the Nc. Accumbens of the AA line, and is of particular functional interest. Within the amygdala, a more loosely inter-related cluster of cytoskeleton-associated genes may point to structural abnormalities. The observed dysregulations may contribute to the alcohol-preferring phenotype.