@article{ref1,
title="The role of orexin signaling in the ventral tegmental area and central amygdala in modulating binge-like ethanol drinking behavior",
journal="Alcoholism: clinical and experimental research",
year="2017",
author="Olney, Jeffrey J. and Navarro, Montserrat and Thiele, Todd E.",
volume="41",
number="3",
pages="551-561",
abstract="BACKGROUND: Recent reports have demonstrated that binge-like ethanol drinking leads to an increase in hypothalamic orexin (OX) signaling and that suppressing this signaling via systemic administration of an orexin receptor (OXR) antagonist blocks this behavior; however, the specific OX pathways that modulate this behavior remain unknown. The goal of the present study was to further elucidate the role of the OX system in binge-like ethanol drinking using behavioral, molecular, and pharmacological techniques. <br><br>METHODS: The drinking-in-the-dark (DID) paradigm was used to model binge-like drinking behavior in male C57BL/6J mice. Experiment 1 examined changes in the OX precursor, prepro-orexin, within the hypothalamus following multiple cycle ethanol or sucrose DID using polymerase chain reaction (PCR) analysis. In experiments 2a & 2b, we used site-directed infusion of an OXR antagonist to examine the individual contribution of each OXR subtype within the ventral tegmental area (VTA) and central amygdala (CeA), repectively, in binge-like ethanol or sucrose drinking. <br><br>RESULTS: Findings from our PCR study revealed that multiple cycles of binge-like ethanol drinking did not lead to changes in prepro-orexin mRNA as a function of binge-like ethanol drinking. However, data from site-directed pharmacology studies indicate that the OX1R is the predominate receptor subtype within the VTA and CeA that regulates binge-like ethanol drinking. Interestingly, inhibition of OX1Rs did not affect binge-like sucrose intake, which suggests that these OX circuits are specific for ethanol consumption. <br><br>CONCLUSIONS: As a whole, these data suggest that the VTA and CeA are important regions in which OX regulates binge-like ethanol drinking behavior. Moreover, these findings identify OXR antagonists as a potential treatment option that may be used to ameliorate problematic drinking behavior while leaving responding to natural rewards relatively intact. This article is protected by copyright. All rights reserved.<br><br>This article is protected by copyright. All rights reserved.<p /> <p>Language: en</p>",
language="en",
issn="0145-6008",
doi="10.1111/acer.13336",
url="http://dx.doi.org/10.1111/acer.13336"
}