title: IL-1 receptor signaling in the basolateral amygdala modulates binge-like ethanol consumption in male C57BL/6J mice.
abstract: Proinflammatory cytokines have been implicated in alcohol-induced neurodegeneration, but the role of the neuroimmune system in alcohol related behaviors has only recently come to the forefront. Herein, the effects of binge-like drinking on IL-1β mRNA and immunoreactivity within the amygdala were measured following the "drinking in the dark" (DID) paradigm, a model of binge-like ethanol drinking in C57BL/6J mice. Moreover, the role of IL-1 receptor signaling in the amygdala on ethanol consumption was assessed. Results indicated that a history of binge-like ethanol drinking promoted a significant increase of IL-1β mRNA expression within the amygdala, and immunohistochemistry analyses revealed that the basolateral amygdala (BLA), but not central amygdala (CeA), exhibited significantly increased IL-1β immunoreactivity. However, Fluoro-Jade® C labeling indicated that multiple cycles of the DID paradigm were not sufficient to elicit neuronal death. Bilateral infusions of IL-1 receptor antagonist (IL-1Ra) reduced ethanol consumption when infused into the BLA but not the CeA. These observations were specific to ethanol drinking as the IL-1Ra did not alter either sucrose drinking or open-field locomotor activity. The current findings highlight a specific role for IL-1 receptor signaling in modulating binge-like ethanol consumption and indicate that proinflammatory cytokines can be induced prior to dependence or any evidence of neuronal cell death. These findings provide a framework in which to understand how neuroimmune adaptations may alter ethanol consumption and therein contribute to alcohol abuse.
authors.affiliation: Department of Psychology & Neuroscience, The University of North Carolina, Chapel Hill, NC 27599, USA; Bowles Center for Alcohol Studies, The University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: S Alex
authors.initials: SA
authors.lastname: Marshall
authors.affiliation: Department of Psychology & Neuroscience, The University of North Carolina, Chapel Hill, NC 27599, USA; Bowles Center for Alcohol Studies, The University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Casachahua
authors.affiliation: Department of Psychology & Neuroscience, The University of North Carolina, Chapel Hill, NC 27599, USA; Bowles Center for Alcohol Studies, The University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Rinker
authors.affiliation: Department of Psychology & Neuroscience, The University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Allyson K
authors.initials: AK
authors.lastname: Blose
authors.affiliation: Department of Psychology & Neuroscience, The University of North Carolina, Chapel Hill, NC 27599, USA; Bowles Center for Alcohol Studies, The University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Donald T
authors.initials: DT
authors.lastname: Lysle
authors.affiliation: Department of Psychology & Neuroscience, The University of North Carolina, Chapel Hill, NC 27599, USA; Bowles Center for Alcohol Studies, The University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: thiele@unc.edu.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Thiele
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000187:drug effects* / Q000378:metabolism*; D063425:Binge Drinking / Q000378:metabolism*; D004660:Encephalitis / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage*; D053583:Interleukin-1beta / Q000378:metabolism*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D053583:Interleukin-1beta; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D000431:Ethanol
keywords: Alcohol abuse; Amygdala; Basolateral amygdala; Binge-like drinking; Cytokines; Drug abuse; Ethanol; IL-1 receptor antagonist; Interleukin-1 beta