well as increasing expression of TLR4 (Alfonso-Loeches et al. 2010). These studies are consistent with ethanol induction of innate immune genes altering behavior and causing neurodegeneration related to addiction. Indomethacin, an anti-inflammatory drug, reduces chronic ethanol induction of brain innate immune genes, particularly in astrocytes, as well as neuronal markers of cell death and addiction-like behavioral dysfunction (Pascual et al. 2007) consistent with innate immune gene induction driving the neurobiology of addiction. Innate immune activation from oxidized phospholipids (Yang et al. 2010), and/or release of damage associated molecular pattern (DAMP) danger sensing molecules, such as high-mobility group box 1 (HMGB1) (Garg et al. 2010), that activate TLR and other signals are likely contributors to innate immune gene induction (Huang et al. 2010)(Fig. 2). Although loops of NF-κB activation are best established in models of alcoholism, all addictive drugs activate NF-κB transcription with the development of addiction (Russo et al. 2009; Loftis et al. 2010). These studies support innate immune gene induction in glia as important contributors to the neurobiology of addiction.
