Oxytocin significantly enhances GABAergic transmission in the central amygdala of alcohol-naïve and alcohol-dependent female rats

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2025-08-08 DOI:10.1016/j.neuropharm.2025.110628

Emaya M. Moss , Enkhzul Batsaikhan , Bryan Cruz , Michael Q. Steinman , Marisa Roberto , Dean Kirson

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引用次数: 0

Abstract

Oxytocin is a promising treatment for alcohol use disorder (AUD) and has been shown to decrease alcohol consumption and withdrawal symptoms associated with alcohol dependence in animal models. Using a rat model of alcohol dependence to investigate oxytocin's effects on dependence-induced alcohol drinking and GABAergic transmission in the central amygdala (CeA), we previously reported that oxytocin blocked escalated alcohol drinking and the acute ethanol-induced enhanced GABA transmission in alcohol-dependent rats. However, these studies were performed only in male rats. We also previously reported sex differences in the effects of alcohol and stress related neuropeptides on CeA GABAergic transmission. Here we examined the effects of oxytocin on CeA GABAergic transmission in naïve and alcohol-dependent female rats, as well as examining sex differences in the expression of components of the oxytocin system. We found that oxytocin increased CeA GABAergic transmission in both naive and alcohol-dependent female rats and this increase was further elevated after the co-application of acute alcohol. We also found that females had fewer oxytocin-expressing neurons in the caudal paraventricular nucleus of the hypothalamus than males, and alcohol-dependent rats had fewer oxytocin-expressing neurons than naïve rats. Further, females had higher numbers of corticotropin releasing factor (Crh) neurons in the CeA, and higher expression levels of Crh and oxytocin receptor mRNA. This research highlights sex differences in pro- and anti-stress system functioning in the CeA in response to acute and chronic alcohol. Sex-specific neuroadaptations in oxytocin signaling may provide a target for more effective therapeutics in the treatment of AUD.

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催产素显著增强alcohol-naïve和酒精依赖雌性大鼠中央杏仁核gaba能的传递

催产素是一种很有前景的治疗酒精使用障碍（AUD）的方法，在动物模型中已被证明可以减少酒精消耗和与酒精依赖相关的戒断症状。利用酒精依赖大鼠模型研究催产素对依赖诱导的饮酒和中央杏仁核（CeA） GABA能传递的影响，我们之前报道过催产素阻断了酒精依赖大鼠的酒精饮酒升级和急性酒精诱导的GABA传递增强。然而，这些研究仅在雄性大鼠中进行。我们之前也报道了酒精和应激相关神经肽对CeA - gaba能传递影响的性别差异。在此，我们研究了催产素对naïve和酒精依赖雌性大鼠中CeA - gaba能传递的影响，并研究了催产素系统成分表达的性别差异。我们发现催产素增加了幼年和酒精依赖雌性大鼠的CeA - gaba能传递，并且在急性酒精联合应用后，这种增加进一步升高。我们还发现，雌性下丘脑尾侧室旁核表达催产素的神经元少于雄性，酒精依赖大鼠表达催产素的神经元少于naïve大鼠。此外，女性在CeA中有更多的促肾上腺皮质激素释放因子（Crh）神经元，Crh和催产素受体mRNA的表达水平更高。这项研究强调了在急性和慢性酒精反应中，CeA的促应激和抗应激系统功能的性别差异。催产素信号的性别特异性神经适应可能为AUD的治疗提供更有效的治疗靶点。

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

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).