Inflammatory immune responses associated with chronic and heavy drinking in mammals have been documented in the liver and the brain, and have been studied largely in the context of alcohol-related disease and tissue damage (Goral et al., 2008). Under these conditions, innate immune signaling, mediated by the Toll-like receptors, can be either suppressed or enhanced, depending on ethanol dose, length of exposure, and tissue type. Recent studies indicate that expression of genes that encode components of the innate immune signaling pathways are also regulated in brain tissue following exposure to moderate levels of ethanol or cocaine. Most consistently, altered expression of transcriptional regulator NFκB was identified in the midbrain following acute and chronic ethanol exposures (Rulten et al., 2006), in whole brains in comparisons of high and low alcohol preferring mouse strains (Mulligan et al., 2006), and in the nucleus accumbens following chronic cocaine exposure (Ang et al., 2001). These studies demonstrate that NFκB signaling pathways are regulated in the brain by drugs of abuse. To date, only 1 functional study for immune pathways in the brain in drug responses
