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Chunk #59 — 4. Discussion

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Activation of inflammatory signaling by lipopolysaccharide produces a prolonged increase of voluntary alcohol intake in mice.
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In summary, these results show that a single injection of LPS produces long-lasting increases in alcohol consumption as well as changes in alcohol-conditioned taste aversion and firing of dopamine neurons in the VTA. Previous results showed altered expression of genes related to neuroimmune signaling in human alcoholics (Liu et al., 2006), rodents with genetic predisposition for alcohol consumption (Mulligan et al., 2006; Saba et al., 2006), and mice and drosophila treated with ethanol (Qin et al., 2008; Kong et al., 2010), and that deletion of immune signaling components decreases alcohol consumption (Blednov et al., in press). Taken together, these results provide strong evidence for neuroimmune regulation of alcohol intake and alcohol aversion as well as the activity of dopaminergic neurons. In view of the ability of alcohol abuse to increase leakage of LPS from the gut and to produce widespread changes in human immune function (Brown et al., 2006; Nelson and Kolls, 2002; Wang et al., 2010), it is possible that activaton of immune signaling may have a role in promoting excessive alcohol consumption in humans.