title: Neuroimmune pathways in alcohol consumption: evidence from behavioral and genetic studies in rodents and humans.
abstract: Immune or brain proinflammatory signaling has been linked to some of the behavioral effects of alcohol. Immune signaling appears to regulate voluntary ethanol intake in rodent models, and ethanol intake activates the immune system in multiple models. This bidirectional link raises the possibility that consumption increases immune signaling, which in turn further increases consumption in a feed-forward cycle. Data from animal and human studies provide overlapping support for the involvement of immune-related genes and proteins in alcohol action, and combining animal and human data is a promising approach to systematically evaluate and nominate relevant pathways. Based on rodent models, neuroimmune pathways may represent unexplored, nontraditional targets for medication development to reduce alcohol consumption and prevent relapse. Peroxisome proliferator-activated receptor agonists are one class of anti-inflammatory medications that demonstrate antiaddictive properties for alcohol and other drugs of abuse. Expression of immune-related genes is altered in animals and humans following chronic alcohol exposure, and the regulatory influences of specific mRNAs, microRNAs, and activated cell types are areas of intense study. Ultimately, the use of multiple datasets combined with behavioral validation will be needed to link specific neuroimmune pathways to addiction vulnerability.
authors.affiliation: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Gizelle
authors.initials: G
authors.lastname: Robinson
authors.affiliation: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA; The Institute for Neuroscience, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Most
authors.affiliation: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA; The Institute for Neuroscience, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Ferguson
authors.affiliation: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Jody
authors.initials: J
authors.lastname: Mayfield
authors.affiliation: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA. Electronic address: harris@austin.utexas.edu.
authors.forename: R Adron
authors.initials: RA
authors.lastname: Harris
authors.affiliation: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Yuri A
authors.initials: YA
authors.lastname: Blednov
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D000818:Animals; D016739:Behavior, Addictive / Q000276:immunology*; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008954:Models, Biological; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology*; D012377:Rodentia; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
chemical_list: D000431:Ethanol
keywords: Dependence; Ethanol; Gene expression; Human alcoholics; Knock-out mice; LPS; PPAR; Preference; TLR4; Two-bottle choice; mRNA; microRNA