Microarray analysis of human postmortem hippocampal tissue revealed large fold-changes in genes associated with interleukin receptor signaling, in particular, up-regulated IL-1 and IL-6 receptors (McClintick et al., 2013). A cascade of events downstream of the IL-1 receptor complex results in the activation of important signaling proteins, such as mitogen-activated kinases (JNK, p38, ERK1/2), as well as transcription factors, including NF-κB (p65 and p50 subunits) and c-Jun (a subunit of AP-1), which control expression of inflammatory and catabolic genes. In contrast, IL-6 receptor signaling occurs primarily via JAK/STAT, resulting in both pro- and anti-inflammatory gene expression. In mice with a genetic predisposition to high alcohol consumption, IL-1 and IL-6 receptor signaling was up-regulated (Mulligan et al., 2006). Differential expression of IL receptors (e.g., IL-6), NF-kB signaling, and chemokine receptors/ligands have also been observed in the hippocampus of cocaine- and alcohol-addicted individuals (Zhou et al., 2011). In addition, bilateral infusions of IL-10 into the basolateral amygdala reduced binge drinking in mice (Marshall et al., 2016). Differential expression of the JAK/STAT pathway was observed in the nucleus accumbens (Mamdani et al., 2015). Alterations
