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

IF 3 Q2 SUBSTANCE ABUSE
Anne M. Dankert, Thomas L. Kash, Todd E. Thiele
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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.

Abstract Image

反复循环饮酒和戒酒会改变雄性和雌性C57BL/6J小鼠前额叶和岛叶皮层、杏仁核和外侧下丘脑的神经肽mRNA。
背景:酗酒是一种危险的酒精(乙醇)消费模式,与各种负面结果相关,包括酒精使用障碍(AUD)的发展。许多神经肽系统被认为在AUD中变得失调;然而,酗酒后反复饮酒和戒酒是否会改变大脑关键区域(如内侧前额叶皮质(mPFC)、岛叶皮质(IC)、杏仁核和外侧下丘脑(LH))的神经肽mRNA,目前尚不清楚。方法:使用“在黑暗中饮酒”(DID)模式,雄性和雌性小鼠分别进行0、3或6个周期的酒精消费。在DID结束后立即收集脑组织,或在禁食24小时后立即收集脑组织,并进行定量聚合酶链反应(qPCR)来评估酗酒样乙醇摄入和禁食的重复循环如何改变22个神经肽相关靶点的相对mRNA表达。结果:我们观察到,酗酒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。其中两种变化是雌性老鼠特有的,而一种是雄性老鼠特有的。结论:这些数据表明神经肽mRNA在脑区和性别依赖的方式中被酗酒样的酒精摄入和戒酒的重复循环所改变。目前的研究结果为探索减少酗酒样乙醇消费和预防AUD发展的潜在目标提供了有用的基础。
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来源期刊
CiteScore
5.40
自引率
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