Genes encoding proteins involved in “immune/stress responses” are one of the most prominent functional groups that exhibit differential gene expression in the frontal cortex between human alcoholics and non-alcoholics (Liu et al., 2006). Expression of these genes in brain is also related to genetic predisposition for alcohol consumption in mice, indicating a role for pro-inflammatory mediators in regulating alcohol intake (Mulligan et al., 2006). Analysis of these gene-expression data sets led to the selection of six genes related to neuroimmune pathways, and behavioral testing of genes selected from these studies showed that null mutant mice lacking selected neuroimmune signaling components drink less alcohol (Blednov et al., in press). Other evidence linking brain neuroimmune or pro-inflammatory signaling to alcohol action includes the finding that long-lasting increases in levels of several pro-inflammatory cytokines were found in rat brain after chronic treatment with high doses of ethanol followed by injection of lipopolysaccharide (LPS) (Qin et al., 2008). Interestingly, one of the cytokines that increased in rat brain, MCP-1 (Ccl2), was also increased in the brain of human alcoholics (He and Crews, 2008). Recently,
