In summary, comparison of three different models of voluntary alcohol consumption in mice shows changes in gene expression in PFC that reveal some similarities, as well as many differences, among the models. Effects on gene expression in liver are more similar for the treatments. Gene expression was also studied one week after injection of LPS and this treatment showed many changes that were similar to ethanol consumption, particularly the CI model. Our data suggest DID is the weakest model of chronic consumption/dependence based on the number of changes in gene expression in PFC, but it remains a relevant model of binge/initiation of drinking which involves activation of brain structures other than PFC. The CI paradigm represents a good model of the neuroimmune component of chronic alcohol consumption as it is most similar to LPS and it reflects some aspects of the strong immune component found in gene expression studies of PFC in human alcoholism. We also provide the first evidence for a connection between immune response, ethanol intake and dopamine signaling in PFC and the CI paradigm provides an approach
