One of the most surprising findings from this work is the distinct effects of the three alcohol treatments on the PFC transcriptome. Despite consuming the same total amount of alcohol, the Chronic and CI groups showed many differences in gene expression. The CI test was originally derived from studies in rats that showed a marked escalation of alcohol consumption with every other day access [23] and CI, but not Chronic, drinking is inhibited by chlorzoxazone [22] indicating differences in the neurobiological mechanisms underlying these two drinking tests. In mice, we found the largest increase in alcohol consumption for the CI group and smaller increases for Chronic and DID drinking during the exposure period (approximately 30 days), which is generally consistent with recent publications [15], [45]. Perhaps because of the greater escalation of consumption in the CI group, the neuroadaptive consequences of every other day access appear to be distinct from continuous access. For example, our cell type analysis indicated changes in expression of genes enriched in oligodendrocytes by CI, but not by Chronic. Most rodent models of excessive or escalating
