Repetitive bouts of binge drinking can lead to neuroplastic events that alter ethanol's pharmacologic effects and perpetuate excessive consumption. The corticotropin-releasing factor (CRF) system is an example of ethanol-induced neuroadaptations that drive excessive ethanol consumption. Our laboratory has previously shown that CRF antagonist, when infused into the central amygdala (CeA), reduces binge-like ethanol consumption. The present study extends this research by assessing the effects of silencing CRF-producing neurons in CeA on binge-like ethanol drinking stemming from "Drinking in the Dark" (DID) procedures. CRF-ires-Cre mice underwent surgery to infuse G_i/o-coupled Designer Receptors Exclusively Activated by Designer Drugs (DREADD) virus or a control virus into either the CeA or basolateral amygdala (BLA). G_i/o-DREADD-induced CRF-neuronal inhibition in the CeA resulted in a 33% decrease in binge-like ethanol consumption. However, no effect on ethanol consumption was seen after DREADD manipulation in the BLA. Moreover, CeA CRF-neuronal inhibition had no effect on sucrose consumption. The effects of silencing CRF neurons in the CeA on ethanol consumption are not secondary to changes in motor function or anxiety-like behaviors as assessed in the open-field test (OFT). Finally, the DREADD construct's functional ability to inhibit CRF-neuronal activity was demonstrated by reduced ethanol-induced c-Fos following DREADD activation. Together, these data suggest that the CRF neurons in the CeA play an important role in binge ethanol consumption and that inhibition of the CRF-signaling pathway remains a viable target for manipulating binge-like ethanol consumption. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

中文翻译：

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中央杏仁核中促肾上腺皮质激素释放因子神经元的化学遗传学抑制改变了雄性小鼠的狂欢样乙醇消耗。

反复发作的暴饮暴食会导致神经塑性事件，从而改变乙醇的药理作用并使过度饮酒永久化。促肾上腺皮质激素释放因子 (CRF) 系统是乙醇诱导的神经适应性驱动过量乙醇消耗的一个例子。我们的实验室之前已经表明，当注入中央杏仁核 (CeA) 时，CRF 拮抗剂可以减少狂欢样的乙醇消耗。本研究通过评估沉默 CeA 中产生 CRF 的神经元对源自“黑暗中饮酒”(DID) 程序的狂欢样乙醇饮酒的影响来扩展这项研究。CRF-ires-Cre 小鼠接受手术以注入 G _i/o由设计药物 (DREADD) 病毒或对照病毒专门激活的耦合设计受体进入 CeA 或基底外侧杏仁核 (BLA)。输入_/输出-CeA 中 DREADD 诱导的 CRF 神经元抑制导致狂欢样乙醇消耗减少 33%。然而，在 BLA 中进行 DREADD 操作后，未观察到对乙醇消耗的影响。此外，CeA CRF 神经元抑制对蔗糖消耗没有影响。沉默 CeA 中的 CRF 神经元对乙醇消耗的影响并不次于运动功能的变化或在开放场测试 (OFT) 中评估的焦虑样行为。最后，DREADD 构建体抑制 CRF 神经元活动的功能能力通过 DREADD 激活后乙醇诱导的 c-Fos 减少得到证明。一起，这些数据表明，CeA 中的 CRF 神经元在酗酒中发挥重要作用，并且抑制 CRF 信号通路仍然是控制类似酗酒的可行目标。（PsycInfo 数据库记录 (c) 2022 APA，保留所有权利）。