Our prior work showed that acute ethanol administration (2 g/kg, 4 hours) induces regionally-selective changes in gene expression in the mesocorticolimbic system [21]. In all profiled brain regions Kerns et al. [22] found the ethanol induced response of these genes was generally markedly different between B6 and D2 mice. The greatest disparity in transcriptional LR was in the prefrontal cortex (PFC), where far more genes were regulated by ethanol in D2 mice than in B6 mice. However, these prior studies on two strains did not have sufficient power for robust definition of gene correlation networks or genetic analysis of mechanisms underlying the ethanol-responsive gene sets.