The chronic intermittent ethanol vapor (CIE) paradigm is known to increase voluntary ethanol consumption in rodents and is considered to be a model of ethanol dependence [22–24]. Recently, Smith and colleagues [25] conducted a time-course experiment examining gene expression in five brain regions following CIE vapor and identified a PFC gene co-expression module enriched with predicted binding sites for several microRNAs that may regulate genes within the module, but microRNA levels were not directly assessed. Previously, we used the CIE model to investigate gene expression changes in three different brain regions (amygdala, AMY; nucleus accumbens, NAC; prefrontal cortex, PFC) at 0, 8 and 120h following exposure to 4 cycles of CIE vapor. These time points represent distinct responses to ethanol exposure, including intoxication (0h), withdrawal (8h) and protracted abstinence (120h). In all brain regions, we identified overlapping time-based gene clusters and gene co-expression modules that shared cell-type specific signatures, perhaps suggesting a common regulatory mechanism. We hypothesized that CIE-induced alterations in microRNA expression could be linked with some of the gene expression changes, enabling us to define the role of microRNAs in gene network changes produced by CIE exposure and withdrawal.