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一个临床前酒精生物样本库:来自行为特征明确的HS大鼠的样本用于酒精使用障碍研究。

A Preclinical Alcohol BioBank: Samples from Behaviorally Characterized HS Rats for AUD Research.

作者信息

Doyle Michelle R, Campo Paola, Dirik Selen, Balaguer Maria G, Martinez Angelica R, Kallupi Marsida, de Guglielmo Giordano

机构信息

Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.

出版信息

bioRxiv. 2025 May 7:2025.04.30.651600. doi: 10.1101/2025.04.30.651600.

DOI:10.1101/2025.04.30.651600
PMID:40654864
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12247670/
Abstract

Alcohol use disorder (AUD) imposes a significant global health burden, yet effective treatments remain limited due to the scarcity of well-characterized biological sample repositories. To address this gap, we established the UCSD Alcohol BioBank, a comprehensive resource containing thousands of samples from over 700 genetically diverse heterogeneous stock (HS) rats. Modeled after successful cocaine and oxycodone biobanks, this repository utilizes the chronic intermittent ethanol vapor exposure (CIE) model, paired with oral self-administration, to characterize AUD-like behaviors, including ethanol consumption, preference, motivation, and withdrawal symptoms such as allodynia and anxiety-like behavior. Longitudinal samples (blood, urine, and feces) are collected before, during, and after ethanol exposure, while terminal samples (brain, heart, liver, kidneys, cecum, reproductive organs, adrenal glands, peripheral blood mononuclear cells) are obtained at intoxication, acute withdrawal, protracted abstinence, or from naive controls. Samples are preserved via snap-freezing or paraformaldehyde fixation to support diverse applications, including genomics, transcriptomics, proteomics, and neuroanatomy. The genetic diversity of HS rats enables genome-wide association studies (GWAS) to identify AUD-related genetic variants. Freely available to non-profit organizations at www.alcoholbiobank.org, with genetic and behavioral data deposited in public repositories, the Alcohol BioBank facilitates collaborative research to uncover biomarkers and develop novel therapies for AUD, addressing a critical need in addiction science.

摘要

酒精使用障碍(AUD)给全球健康带来了重大负担,但由于缺乏特征明确的生物样本库,有效的治疗方法仍然有限。为了填补这一空白,我们建立了加州大学圣地亚哥分校酒精生物样本库,这是一个综合性资源库,包含来自700多只基因多样的异质种群(HS)大鼠的数千份样本。该样本库以成功的可卡因和羟考酮生物样本库为模型,采用慢性间歇性乙醇蒸汽暴露(CIE)模型,并结合口服自我给药,来表征类似AUD的行为,包括乙醇消耗、偏好、动机以及诸如痛觉过敏和焦虑样行为等戒断症状。在乙醇暴露之前、期间和之后收集纵向样本(血液、尿液和粪便),而在中毒、急性戒断、长期禁欲时或从未接触过乙醇的对照组中获取终末样本(脑、心脏、肝脏、肾脏、盲肠、生殖器官、肾上腺、外周血单核细胞)。样本通过速冻或多聚甲醛固定保存,以支持包括基因组学、转录组学、蛋白质组学和神经解剖学在内的多种应用。HS大鼠的基因多样性使得全基因组关联研究(GWAS)能够识别与AUD相关的基因变异。酒精生物样本库在www.alcoholbiobank.org上向非营利组织免费开放,其遗传和行为数据存于公共数据库中,有助于开展合作研究以发现生物标志物并开发针对AUD的新疗法,满足了成瘾科学领域的一项关键需求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/12247670/6dc86cee15d9/nihpp-2025.04.30.651600v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/12247670/7304f822fecc/nihpp-2025.04.30.651600v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/12247670/c74c4cbc433d/nihpp-2025.04.30.651600v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/12247670/609b6f4f35d3/nihpp-2025.04.30.651600v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/12247670/6dc86cee15d9/nihpp-2025.04.30.651600v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/12247670/7304f822fecc/nihpp-2025.04.30.651600v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/12247670/c74c4cbc433d/nihpp-2025.04.30.651600v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/12247670/609b6f4f35d3/nihpp-2025.04.30.651600v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/920f/12247670/6dc86cee15d9/nihpp-2025.04.30.651600v1-f0004.jpg

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本文引用的文献

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Genetic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats.影响异质种群大鼠线索反应性的基因位点。
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Genome-wide association study reveals multiple loci for nociception and opioid consumption behaviors associated with heroin vulnerability in outbred rats.全基因组关联研究揭示了远交系大鼠中与海洛因易感性相关的伤害感受和阿片类药物消费行为的多个基因座。
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Large-scale characterization of cocaine addiction-like behaviors reveals that escalation of intake, aversion-resistant responding, and breaking-points are highly correlated measures of the same construct.大规模描述可卡因成瘾样行为揭示,摄入量增加、对厌恶刺激的抵抗反应和觅药行为的临界点是同一结构的高度相关测量指标。
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