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Chunk #21 — Innate immune gene expression in brain changes behavior

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Induction of innate immune genes in brain create the neurobiology of addiction.
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Drug consumption is also linked to innate immune gene expression. Addictionlike drinking behavior in rats and mice associates with increased NF-κB, its regulatory proteins and innate immune genes (Mulligan et al. 2006). Interestingly, microglobulin (β2M) an NF-κB target gene involved in microglial MHC immune signaling (Pahl 1999) shows the largest increase in high alcohol preferring brain transcriptomes (Mulligan et al. 2006). Innate immune gene induction in multiple mouse studies finds induction suppression through transgenic knock outs associates with increased drinking or decreased drinking respectively across strains of mice. These studies further support the role of these genes in regulating excessive addiction like drug consumption (Blednov et al. 2005; Blednov 2010). A single injection of LPS is able to produce a long-lasting increase in alcohol consumption (Blednov 2011) that corresponds to persistent increases in brain innate immune gene expression (Qin et al. 2007). These findings are consistent with innate immune gene expression driving addiction like behavior, both excessive consumption and the negative-affect, anxiety and depression-like behaviors of addiction.