The Role of Cytokines in Binge-like Ethanol Consumption and Ethanol-induced Sedation Public Deposited

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  • March 20, 2019
Creator
  • Casachahua, John
    • Affiliation: College of Arts and Sciences, Department of Psychology and Neuroscience
Abstract
  • There is a growing body of research that is establishing a prominent role for the immune system in the brain. Recent studies have demonstrated a role for immune system messenger cytokines in modulating binge-like ethanol consumption. The goal of this dissertation is to examine the roles of proinflammatory cytokines, specifically IL-6, in binge-like ethanol consumption and ethanol-induced sedation. The experiments of Chapter 2 characterized the expression of IL-6 in the central amygdala, paraventricular nucleus of the hypothalamus (PVN), and other candidate regions of the brain in response to binge-like ethanol consumption through use of the “Drinking in the Dark” (DID) protocol followed by immunohistochemical procedures examining IL-6 immunoreactivity in the candidate regions of the brain. The most promising region of interest was the central amygdala (CEA), and in Chapter 3, experiments were performed with site-directed infusions of IL-6 receptor antagonist into the CEA to alter proinflammatory cytokine signaling and modulate binge-like ethanol consumption. These IL-6 receptor antagonists that were site-specifically administered on the test day on the third cycle of the DID protocol with ethanol reduced binge-like ethanol consumption. Following up on these findings were sucrose DID tests that were used to determine that consumption in general was not reduced by the application of this cytokine antagonist. Chapter 4 describes the experiments that were run to assess whether IL-6 specifically modulated ethanol’s sedative/ataxic properties, through the use of site-directed infusions of IL-6 receptor antagonist employed to alter proinflammatory cytokine signaling in the central amygdala. Mice were exposed to an intraperitoneal ethanol administration followed by the application of the IL-6 receptor antagonist. Subsequent to this protocol, mice were tested on their motor reflexes with a rotarod apparatus to determine the antagonist’s impact on ethanol-induced sedation. Here it was established that IL-6 does not appear to modulate ethanol’s sedative/ataxic properties. Together, these experiments indicate that IL-6 signaling critically modulates binge-like ethanol consumption after a history of binge-like ethanol consumption. The results suggest a potential therapeutic value for IL-6 antagonism in the reduction of binge ethanol drinking and a prophylactic approach against ethanol dependence.
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  • In Copyright
Advisor
  • Jones, Deborah
  • Reissner, Kathryn
  • Thiele, Todd
  • Carelli, Regina
  • Lysle, Donald
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016
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