title: Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala.
abstract: Excessive ethanol consumption alters the neuroimmune system and particularly impacts the cytokine milieu of the CNS. Cytokine dysregulation has been shown to underlie addictive-like behaviors including alcohol abuse; however, many studies focus primarily on the proinflammatory cytokine profile during alcohol dependence. The current study furthers this research by determining the impact of excessive ethanol consumption on interleukin-10 (IL-10) and interleukin-4 (IL-4) activity in a model of non-dependent binge consumption called the "drinking in the dark" (DID) paradigm. Furthermore, the ability of IL-10 to modulate ethanol consumption was tested using site-directed pharmacology. Immunohistochemistry analyses determined that ethanol decreased IL-10 by 50 % in the basolateral amygdala (BLA) but had no effect on IL-4. Neither IL-10 nor IL-4, however, were altered in the central amygdala (CEA). Enzyme linked immunosorbent assays confirmed that IL-10 was decreased in the amygdala but not in the serum, suggesting changes of this cytokine with the DID paradigm are restricted to the central nervous system. Finally, bilateral infusions of IL-10 into the BLA, but not CeA, reduced binge-like drinking and corresponding blood ethanol concentrations without impacting either locomotor activity or anxiety-like behavioral correlates. Together, these data support the idea that alcohol abuse dysregulates specific anti-inflammatory cytokines; however, ameliorating alcohol-induced effects on cytokines, like IL-10, may prove to be an effective therapy in curbing excessive consumption.
authors.affiliation: Department of Psychology & Neuroscience, The University of North Carolina, Davie Hall, CB# 3270, Chapel Hill, NC, 27599-3270, 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, Davie Hall, CB# 3270, Chapel Hill, NC, 27599-3270, USA.
authors.forename: Kyle H
authors.initials: KH
authors.lastname: McKnight
authors.affiliation: Department of Psychology & Neuroscience, The University of North Carolina, Davie Hall, CB# 3270, Chapel Hill, NC, 27599-3270, USA.
authors.forename: Allyson K
authors.initials: AK
authors.lastname: Blose
authors.affiliation: Department of Psychology & Neuroscience, The University of North Carolina, Davie Hall, CB# 3270, Chapel Hill, NC, 27599-3270, 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, Davie Hall, CB# 3270, Chapel Hill, NC, 27599-3270, USA. thiele@unc.edu.|Bowles Center for Alcohol Studies, The University of North Carolina, Chapel Hill, NC, 27599, USA. thiele@unc.edu.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Thiele
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D063425:Binge Drinking / Q000276:immunology / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage*; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10; D000431:Ethanol
keywords: Alcohol abuse; Amygdala; Binge drinking; Cytokines; Drinking in the dark paradigm; Interleukin-10; Interleukin-4; Neuroimmune system