Acute Ethanol Significantly Enhances GABAergic Transmission in the Central Lateral Amygdala of Alcohol-Naïve and Alcohol-Dependent Male Rats

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.) Pub Date : 2026-04-07 DOI:10.1111/acer.70290

Emaya M. Moss, Enkhzul Batsaikhan, Samantha Amsden, Dean Kirson

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Abstract

Background

The central nucleus of the amygdala (CeA), a key component of the extended amygdala, is critical for mediating behavioral and physiological responses to stress and alcohol exposure. While extensive research has characterized alcohol's effects on GABAergic transmission in the medial CeA (CeM), the lateral CeA (CeL) remains underexplored, despite its central role in upstream signaling within the CeA circuit.

Methods

In this study, we examined the effects of acute ethanol (EtOH) on GABAergic transmission in the CeL of alcohol-naïve and alcohol-dependent male and female Wistar rats. Alcohol dependence was induced using a chronic intermittent ethanol vapor exposure protocol. Whole-cell patch-clamp recordings were conducted on CeL neurons to measure spontaneous inhibitory postsynaptic currents (sIPSCs) at baseline and following acute application of 44 mM EtOH.

Results

Acute EtOH significantly increased sIPSC frequency in CeL neurons from male rats, regardless of alcohol history, indicating enhanced presynaptic GABA release. In contrast, female rats showed no significant changes in sIPSC frequency or amplitude following acute EtOH application, whether alcohol-naïve or dependent. Several neuronal properties—including membrane resistance, holding current, and rheobase—were significantly altered in alcohol-dependent females. However, overall spiking characteristics and baseline inhibitory transmission did not differ significantly between naïve and dependent groups within each sex.

Conclusions

These findings reveal, for the first time, that acute EtOH produces sex-specific effects on GABAergic transmission in the CeL, enhancing inhibitory signaling in males but not females. This pattern mirrors previous observations in the CeM and underscores the importance of including both sexes in alcohol research. Understanding the mechanisms underlying these differences may inform the development of sex-specific treatments for alcohol use disorder.

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急性乙醇显著增强Alcohol-Naïve和酒精依赖雄性大鼠中央外侧杏仁核gaba能传递。

背景：杏仁核中央核（CeA）是扩展杏仁核的关键组成部分，在介导应激和酒精暴露的行为和生理反应中起关键作用。尽管广泛的研究表明酒精对内侧CeA （CeM）中gaba能传递的影响，但外侧CeA （CeL）仍未得到充分研究，尽管它在CeA回路的上游信号传导中起着核心作用。方法：在本研究中，我们检测了急性乙醇（EtOH）对alcohol-naïve和酒精依赖的雄性和雌性Wistar大鼠细胞中gaba能传递的影响。采用慢性间歇乙醇蒸气暴露方案诱导酒精依赖。对细胞神经元进行全细胞膜片钳记录，以测量基线和急性应用44 mM EtOH后自发抑制性突触后电流（sIPSCs）。结果：急性EtOH显著增加雄性大鼠细胞神经元sIPSC频率，无论酒精史如何，表明突触前GABA释放增强。相比之下，雌性大鼠在急性EtOH应用后sIPSC频率或振幅没有明显变化，无论是alcohol-naïve还是依赖。在酒精依赖的女性中，一些神经元特性——包括膜阻力、保持电流和流变酶——发生了显著改变。然而，在naïve和不同性别的依赖组之间，总体峰值特征和基线抑制传播没有显着差异。结论：这些发现首次揭示了急性EtOH对细胞中gaba能传递产生性别特异性影响，增强了雄性而非雌性的抑制信号。这一模式反映了以前在CeM中的观察结果，并强调了在酒精研究中包括两性的重要性。了解这些差异背后的机制可能会为酒精使用障碍的性别特异性治疗提供信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alcohol (Hanover, York County, Pa.)

CiteScore

5.40

自引率

0.00%

发文量