There is strong evidence for a neuroinflammatory response, with NFκB and multiple cytokines activated, altering expression of many of their downstream targets including the acute phase response pathway. Chronic alcoholics are known to have highly activated NFκB signaling in the hippocampus (McClintick et al., 2013) and NFκB can be instrumental in the addiction process (Crews et al., 2011). There is evidence for increased oxidative stress which can accompany inflammatory responses (Table 4). There were also indications of an inflammatory response in the Acb-sh of these animals but not the CeA (McBride et al., 2014) with acute phase signaling and the IL-2 pathway altered in Acb-sh. The overlap analysis with the human data (Figure 2, Supplementary Tables 1 & 5) supports previous findings that both oxidative stress and inflammation are important factors in alcohol use disorders in humans.
