A number of studies suggest astrocytes and microglia are activated in addiction. Using both in vitro and in vivo models through a series of elegant studies Guerri's laboratory has clearly established that chronic ethanol treatment induces astroglial activation and astrogliosis in brain as indicated by marked upregulation of GFAP immunoreactivity within hypertrophic astrocytes, (Wilhelmsson et al. 2006; Chvatal et al. 2007; Gomez-Pinedo et al. 2008). TLR are pattern recognition receptors that activate NF-κB transcription. TLR and interleukin-1 receptors are expressed on microglia and other cells during innate immune activation contributing to amplification of signaling. Recently TLR4 was discovered to contribute to persistent innate immune gene induction and neurodegeneration by ethanol (Alfonso-Loeches et al. 2010). Guerri's studies indicate that chronic ethanol upregulation and activation of TLR4-MyD88-glial NF-κB signaling contributes to alcohol induced neurodegeneration. Acute alcohol activates TLR4 signaling to NF-κB as 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
