Discrepancies between brain regions also arose from models of chronic ethanol exposure. The effect of two series of four cycles of intermittent ethanol vapor inhalation one week apart, a paradigm known to induce physical dependence [66] and ethanol self-administration escalation [67], was analyzed in the prefrontal cortex, hippocampus and nucleus accumbens of C57Bl/6J mice [30]. Transcriptional disruption was strikingly stronger in the prefrontal cortex than in other brain regions at the end of chronic ethanol exposure, as previously found in rats exposed to two weeks of chronic intermittent ethanol inhalation [31]. Functional clustering of the 284 genes regulated in the prefrontal cortex highlighted the Ras/MAPK and notch signaling pathways, as well as ubiquitination. The hippocampus, on the other hand, exhibited a much higher transcriptional responsiveness during acute withdrawal, and several of the 139 regulated genes were associated with mRNA processing and actin dynamics. Genes governing circadian rhythms were over-represented among the few genes that were affected in the nucleus accumbens under both conditions. Interestingly, while the nucleus accumbens of C57Bl/6J mice was more responsive than prefrontal cortex to an acute
