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Affiliation
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Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA. |
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Abstract
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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.
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.
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.
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.
This article is protected by copyright. All rights reserved.
Language: en |