In response to alcohol, several microglial proteins are differentially regulated across multiple brain regions. Genetic deletion of monocyte chemoattractant protein (MCP-1/CCL2), a microglial-derived chemokine, decreases drinking and alcohol preference in mice (Blednov et al. 2005). In another preclinical study, overexpression of MCP-1/CCL2 preserved long-term potentiation and fear conditioning with alcohol exposure (Bray et al. 2013). MCP-1/ CCL2 expression is also globally increased in postmortem brain homogenates from alcohol-dependent subjects (He et al. 2008). In the cingulate cortex, ionized calcium binding adaptor protein-1 (Iba-1) and glucose transporter-5 are increased in alcoholics relative to healthy controls (He et al. 2008). In the VTA and thalamus, however, glucose transporter-5 expression is elevated, but Iba-1 expression is unaffected. Finally, in the amygdala, no microglial marker differences were observed in alcoholics relative to healthy volunteers (He et al. 2008). In addition to these activation markers, alcohol affects the expression of microglial cell surface receptors. Acute alcohol administration induces Toll-like receptor (TLR)4/type I interleukin (IL)-1 receptor signaling mediators: nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen activated protein kinase signal transduction cascades (Blanco et
