Chronic ethanol exposure reduces resting state functional connectivity and regional synchrony in male rats.

IF 3.3 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2025-08-19 DOI:10.1007/s00213-025-06881-0

Elizabeth J Crofton, Sung-Ho Lee, Woomi Ban, Tzu-Wen Winnie Wang, Yen-Yu Ian Shih, A Leslie Morrow, Melissa A Herman

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引用次数: 0

Abstract

Rationale: Alcohol use disorder (AUD) is a common mental health disorder affecting many individuals and their families in the United States. The effects of alcohol are not fully understood, particularly the effect of alcohol on baseline brain activity.

Objectives: We aimed to assess whether chronic ethanol exposure alters resting state functional connectivity between regions of interest (ROIs) previously associated with addiction in male rats. We also aimed to assess whether inhibition of histone deacetylases (HDAC) reduced or blocked the effects of chronic ethanol exposure. Finally, we aimed to investigate whether chronic ethanol exposure altered regional homogeneity (ReHo) and whether HDAC inhibition blocked the effects of ethanol on ReHo.

Methods: Male rats were administered water or ethanol (5 g/kg, 25% v/v) via intragastric gavage once daily during the light cycle for 14 days and allowed to withdraw for 24 h. Rats were additionally injected with either the HDAC inhibitor trichostatin A (TSA) (2 mg/kg, i.p.) or vehicle (10% DMSO in 0.9% saline) on the last two days of gavage and on the last day of withdrawal. Rats were scanned with magnetic resonance imaging (MRI) to obtain an anatomical scan as well as resting state functional connectivity (rs-fMRI).

Results: We found that chronic ethanol exposure decreased rs-fMRI in the following pairs of ROIs: caudate putamen-prelimbic cortex, caudate putamen-infralimbic cortex, caudate putamen-nucleus accumbens core as well as caudate putamen-insula, insula-prelimbic cortex, and insula-infralimbic cortex. Chronic ethanol exposure also decreased ReHo, particularly in the dorsal striatum. We did not find significant effects of inhibition of HDACs on rs-fMRI of ROIs or ReHo.

Conclusions: Chronic alcohol exposure and withdrawal decreases baseline functional connectivity and local synchrony in male rats which is not affected by HDAC inhibition. Future studies should examine the effects of alcohol on resting state connectivity in female rats as well as in voluntary alcohol consumption paradigms. Understanding baseline differences may open new therapeutic avenues in alcohol abuse and AUD to restore typical resting state connectivity.

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慢性乙醇暴露降低雄性大鼠静息状态功能连通性和区域同步。

理由：在美国，酒精使用障碍（AUD）是一种常见的精神健康障碍，影响着许多个人及其家庭。酒精的影响还没有被完全了解，尤其是酒精对基线大脑活动的影响。目的：我们旨在评估慢性乙醇暴露是否会改变雄性大鼠先前与成瘾相关的兴趣区域（roi）之间的静息状态功能连接。我们还旨在评估组蛋白去乙酰化酶（HDAC）的抑制是否会减少或阻断慢性乙醇暴露的影响。最后，我们的目的是研究慢性乙醇暴露是否改变了区域均匀性（ReHo），以及HDAC抑制是否阻断了乙醇对ReHo的影响。方法：雄性大鼠在光照周期内每天1次灌胃水或乙醇（5 g/kg, 25% v/v），连续14天，停药24 h。大鼠在灌胃的最后两天和停药的最后一天分别注射HDAC抑制剂曲古抑素A (TSA) （2 mg/kg, i.p）或载药（10% DMSO加入0.9%生理盐水）。用磁共振成像（MRI）对大鼠进行扫描，获得解剖扫描和静息状态功能连接（rs-fMRI）。结果：我们发现慢性乙醇暴露降低了以下对roi的rs-fMRI：尾状壳核-边缘前皮质、尾状壳核-边缘下皮质、尾状壳核-伏隔核核心以及尾状壳核-岛、岛-边缘前皮质和岛-边缘下皮质。慢性乙醇暴露也降低了ReHo，特别是在背纹状体。我们没有发现抑制hdac对ROIs或ReHo的rs-fMRI有显著影响。结论：慢性酒精暴露和戒断会降低不受HDAC抑制影响的雄性大鼠的基线功能连通性和局部同步性。未来的研究应该检查酒精对雌性大鼠静息状态连接的影响，以及在自愿饮酒模式下的影响。了解基线差异可能为酒精滥用和AUD的治疗开辟新的途径，以恢复典型的静息状态连通性。

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

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.