An Examination of the Role of the Central Orexin System in Binge-Like Ethanol Consumption
Public Deposited- Last Modified
- March 21, 2019
- Creator
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Olney, Jeffrey
- Affiliation: College of Arts and Sciences, Department of Psychology and Neuroscience
- Abstract
- Although centrally synthesized exclusively within the hypothalamus, orexin (OX) neurons project to various structures throughout the brain to modulate a host of physiological functions, including reward processing and stress responding, each of which contributes to the likelihood that an individual may drink ethanol. More recent evidence has also implicated this system in modulating the neurobiological responses to ethanol. The goal of the present dissertation was to further examine the role of the OX system in neurobiological responses to ethanol by characterizing the participation of this peptide system in binge-like ethanol drinking behavior. We assessed the impact of repeated episodes of binge-like ethanol drinking on different aspects of the OX system in Chapter 2 and found that binge-like ethanol drinking caused evidence of increased OX signaling, particularly within the lateral hypothalamus (LH), but did not produce lasting changes in mRNA expression. In Chapter 3, we used site-directed pharmacological tools to examine the individual contribution of each OX receptor, the OX1R and OX2R, within the ventral tegmental area (VTA) in binge-like ethanol drinking. Here, we observed that signaling onto the OX1R, but not OX2R, selectively modulates binge-like ethanol drinking without affecting sucrose consumption. Moreover, further investigations revealed that it does so independent of stress modulation as inhibiting intra-VTA OX1Rs did not alter anxiety-like behavior. Similarly, Chapter 4 was designed to characterize the participation of each OXR within the central nucleus of the amygdala (CeA). Using selective antagonists directly infused into the CeA, we found that binge-like ethanol drinking within this region is predominately regulated by the OX1R and that this circuitry is independent of that which modulates responding to natural reinforcers and stress as inhibiting OX1Rs within the CeA did not affect binge-like sucrose consumption nor did it alter anxiety-like behavior. Together, these data indicate that the OX system significantly contributes to binge-like ethanol drinking and reveal that the LH→VTA and LH→CeA are two key pathways that selectively modulate this behavior. More broadly, these findings implicate the OX system as a highly promising target for the treatment of alcohol use disorders.
- Date of publication
- May 2016
- Keyword
- DOI
- Resource type
- Rights statement
- In Copyright
- Advisor
- Thiele, Todd
- Lysle, Donald
- Reissner, Kathryn
- Carelli, Regina
- Daughters, Stacey
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill Graduate School
- Graduation year
- 2016
- Language
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