In order to extract and dissect acute ethanol-responsive gene networks, we performed a large-scale gene expression analysis across recombinant inbred (RI) strains derived from the B6×D2 (BXD) genetic mapping panel. The BXD family has been widely used for both genetic studies on ethanol behaviors and many other phenotypes, and for expression genetics studies [10]. For each included BXD strain, we profiled PFC, ventral midbrain (VMB) and nucleus accumbens (NAc) transcriptomes of mice from saline and ethanol treatment groups. This produced the most extensive assessment of ethanol-responsive brain gene expression to date. Furthermore, we focused on PFC and produced the first genetic analysis of ethanol-responsive gene networks. Our results show network-level enrichment of genes involved in synaptic plasticity and identify key hub genes regulating the ethanol response for large networks of genes. This first such detailed genetic analysis of the acute “ethanol responsome” may provide valuable insight for molecular mechanisms underlying the neurobiology of ethanol and also ultimately provide novel AUD susceptibility candidate genes and targets for intervention in alcoholism.
