Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093.
Center for Medical Genetics Ghent, Ghent University, Ghent 9000, Belgium.
eNeuro. 2021 Jun 17;8(3). doi: 10.1523/ENEURO.0033-21.2021. Print 2021 May-Jun.
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/.
大鼠羟考酮和可卡因生物库包含通过基因型(使用遗传多样性的基因分型 HS 大鼠)、表型(在先进的 SA 模型中测量成瘾样行为)、时间点(在 SA 之前、期间和之后以及成瘾周期的三个不同时间点(陶醉、戒断和禁欲或不接触药物的情况下通过年龄匹配的幼稚大鼠)进行纵向收集)、样本收集(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)的样品。物质使用障碍(SUDs)在我们的社会中普遍存在,对个人和社会经济造成了巨大的损失。在确定生物标志物和新的药物开发靶点方面的一个关键障碍是缺乏用于获得具有 SUD 详细行为特征的生物样本的资源。此外,几乎不可能找到纵向样本。作为正在进行的两个异质品系(HS)大鼠大型行为遗传研究的一部分,我们使用经过充分验证的静脉内可卡因和羟考酮自我给药(SA)的长通道(LgA)模型以及成瘾相关行为的全面特征建立了两个临床前生物库。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强迫反应脆弱或有弹性的个体。在整个实验过程中,在接触药物之前、陶醉时、急性戒断时和长期禁欲时收集纵向样本,并包括幼稚的、年龄匹配的对照。样本包括但不限于血浆、粪便和尿液、全脑、脑切片和打孔、肾脏、肝脏、脾脏、卵巢、睾丸和肾上腺。使用三种保存方法(固定在甲醛中、速冻或冷冻保存)来促进多种下游应用,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、生物标志物发现和其他细胞和分子方法。迄今为止,已经从 1000 多个独特的动物中收集了超过 20000 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。