The Cocaine and Oxycodone Biobanks, Two Repositories from Genetically Diverse and Behaviorally Characterized Rats for the Study of Addiction
The Cocaine and Oxycodone Biobanks, Two Repositories from Genetically Diverse and Behaviorally Characterized Rats for the Study of Addiction
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DOI：
10.1523/eneuro.0033-21.2021
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发表时间：
2021-05-01
期刊：
影响因子：
3.4
通讯作者：
Geprge, Olivier
中科院分区：
文献类型：
--
作者：
Carrette, Lieselot L. G.;de Guglielmo, Giordano;Geprge, Olivier
大鼠羟考酮和可卡因生物库包含因基因型而异的样本（通过使用遗传多样的基因型HS大鼠），表型（通过在高级SA模型中测量成瘾样行为），时间点（在SA之前、期间和之后纵向收集样品，并在成瘾周期的三个不同时间点终末收集样品：中毒、戒断和禁欲或未暴露于药物（通过年龄匹配的未处理大鼠），采集样本（器官、细胞、生物流体、粪便）、保存（多聚甲醛固定、速冻或冷冻保存）和应用（蛋白质组学、转录组学、微生物组学、代谢组学、表观遗传学、解剖学、电路分析、生物标志物发现等。物质使用障碍（SUD）在我们的社会中普遍存在，并且具有巨大的个人和社会经济成本。在确定生物标志物和药物开发的新靶点方面的一个关键障碍是缺乏获得具有SUD详细行为特征的生物样品的资源。此外，几乎不可能找到纵向样本。作为两个正在进行的大规模行为遗传学研究的一部分，在异质性股票（HS）大鼠，我们已经创建了两个临床前的生物库，使用经过充分验证的长期访问（LGA）模型静脉内可卡因和羟考酮自我管理（SA）和成瘾相关行为的综合表征。HS大鼠的遗传多样性模拟了人类群体的多样性，包括对可卡因或羟考酮的强迫样反应脆弱或有弹性的个体。在整个实验过程中，在暴露于药物之前，在中毒期间，急性戒断和长期禁欲期间收集纵向样品，并包括幼稚的，年龄匹配的对照。样品包括但不限于血浆、粪便和尿液、全脑、脑切片和穿孔物、肾、肝、脾、卵巢、睾丸和肾上腺。三种保存方法（固定在甲醛中，速冻或冷冻保存）用于促进不同的下游应用，如蛋白质组学，代谢组学，转录组学，表观基因组学，微生物组学，神经解剖学，生物标志物发现，以及其他细胞和分子方法。到目前为止，已经从1000多种独特的动物中收集了超过20，000个样本，并通过https://www.cocainebiobank.org/和https://www.oxycodonebiobank.org/免费提供给非营利机构。
The rat oxycodone and cocaine biobanks contain samples that vary by genotypes (by using genetically diverse genotyped HS rats), phenotypes (by measuring addiction-like behaviors in an advanced SA model), timepoints (samples are collected longitudinally before, during, and after SA, and terminally at three different timepoints in the addiction cycle: intoxication, withdrawal, and abstinence or without exposure to drugs through age-matched naive rats), samples collected (organs, cells, biofluids, feces), preservation (paraformaldehyde-fixed, snap-frozen, or cryopreserved) and application (proteomics, transcriptomics, microbiomics, metabolomics, epigenetics, anatomy, circuitry analysis, biomarker discovery, etc. Substance use disorders (SUDs) are pervasive in our society and have substantial personal and socioeconomical costs. A critical hurdle in identifying biomarkers and novel targets for medication development is the lack of resources for obtaining biological samples with a detailed behavioral characterization of SUD. Moreover, it is nearly impossible to find longitudinal samples. As part of two ongoing large-scale behavioral genetic studies in heterogeneous stock (HS) rats, we have created two preclinical biobanks using well-validated long access (LgA) models of intravenous cocaine and oxycodone self-administration (SA) and comprehensive characterization of addiction-related behaviors. The genetic diversity in HS rats mimics diversity in the human population and includes individuals that are vulnerable or resilient to compulsive-like responding for cocaine or oxycodone. Longitudinal samples are collected throughout the experiment, before exposure to the drug, during intoxication, acute withdrawal, and protracted abstinence, and include naive, age-matched controls. Samples include, but are not limited to, blood plasma, feces and urine, whole brains, brain slices and punches, kidney, liver, spleen, ovary, testis, and adrenal glands. Three preservation methods (fixed in formaldehyde, snap-frozen, or cryopreserved) are used to facilitate diverse downstream applications such as proteomics, metabolomics, transcriptomics, epigenomics, microbiomics, neuroanatomy, biomarker discovery, and other cellular and molecular approaches. To date, >20,000 samples have been collected from over 1000 unique animals and made available free of charge to non-profit institutions through https://www.cocainebiobank.org/ and https://www.oxycodonebiobank.org/.