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雄性和雌性C57BL/6J小鼠反复进行类似暴饮暴食的乙醇摄入和戒酒循环,会改变前额叶和岛叶皮质、杏仁核以及下丘脑外侧的神经肽mRNA。

Repeated cycles of binge-like ethanol consumption and abstinence alter neuropeptide mRNA in prefrontal and insular cortex, amygdala, and lateral hypothalamus of male and female C57BL/6J mice.

作者信息

Dankert Anne M, Kash Thomas L, Thiele Todd E

机构信息

Department of Psychology & Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

The Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

出版信息

Alcohol Clin Exp Res (Hoboken). 2025 Mar;49(3):573-586. doi: 10.1111/acer.15536. Epub 2025 Jan 31.

DOI:10.1111/acer.15536
PMID:39888221
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11928273/
Abstract

BACKGROUND

Binge drinking is a risky pattern of alcohol (ethanol) consumption associated with a variety of negative outcomes, including the development of alcohol use disorder (AUD). Many neuropeptide systems are thought to become dysregulated in AUD; however, whether repeated cycles of binge-like ethanol consumption and abstinence following binge-like drinking alter neuropeptide mRNA in key brain regions, such as the medial prefrontal cortex (mPFC), insular cortex (IC), amygdala, and lateral hypothalamus (LH), remains unknown.

METHODS

Male and female mice underwent 0, 3, or 6 cycles of binge-like ethanol consumption using the "Drinking in the Dark" (DID) paradigm. Brain tissue was collected either immediately following the final session of DID or after a 24-h period of abstinence, and quantitative polymerase chain reaction (qPCR) was performed to assess how repeated cycles of binge-like ethanol intake and abstinence alter relative mRNA expression for 22 neuropeptide-related targets.

RESULTS

We observed that repeated cycles of binge-like ethanol consumption and abstinence altered relative mRNA expression for 11 targets in the mPFC, five targets in the IC, eight targets in the amygdala, and two targets in the LH. Two of these alterations were specific to female mice, while one was specific to male mice.

CONCLUSIONS

These data suggest that neuropeptide mRNA is altered by repeated cycles of binge-like ethanol intake and abstinence in a brain region and sex-dependent manner. The current findings provide a useful foundation from which to explore potential targets to decrease binge-like ethanol consumption and prevent the development of AUD.

摘要

背景

暴饮是一种危险的酒精(乙醇)消费模式,与多种负面后果相关,包括酒精使用障碍(AUD)的发展。许多神经肽系统被认为在酒精使用障碍中会失调;然而,在暴饮样饮酒后反复进行暴饮样乙醇消费和戒酒的循环是否会改变关键脑区(如内侧前额叶皮质(mPFC)、岛叶皮质(IC)、杏仁核和外侧下丘脑(LH))中的神经肽mRNA,仍然未知。

方法

使用“黑暗中饮酒”(DID)范式,对雄性和雌性小鼠进行0、3或6个周期的暴饮样乙醇消费。在DID的最后一次实验后立即或在24小时戒酒期后收集脑组织,并进行定量聚合酶链反应(qPCR),以评估暴饮样乙醇摄入和戒酒的反复循环如何改变22个神经肽相关靶点的相对mRNA表达。

结果

我们观察到,暴饮样乙醇消费和戒酒的反复循环改变了mPFC中11个靶点、IC中5个靶点、杏仁核中8个靶点和LH中2个靶点的相对mRNA表达。其中两种改变是雌性小鼠特有的,而一种是雄性小鼠特有的。

结论

这些数据表明,神经肽mRNA在脑区和性别依赖性方式上会因暴饮样乙醇摄入和戒酒的反复循环而改变。目前的研究结果为探索减少暴饮样乙醇消费和预防酒精使用障碍发展的潜在靶点提供了有用的基础。

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本文引用的文献

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Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) of the Bed Nucleus of the Stria Terminalis Mediates Heavy Alcohol Drinking in Mice.终纹床核脑啡肽(PACAP)介导小鼠的重度酒精摄入。
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Neurotensin and Alcohol Use Disorders: Towards a Pharmacological Treatment.神经降压素与酒精使用障碍:走向药物治疗。
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