Oxycodone Neonatal Opioid Withdrawal Syndrome and Adult Abuse Liability

羟考酮新生儿阿片类药物戒断综合征和成人滥用责任

基本信息

批准号：
10838025
负责人：
ELIZABETH M BYRNES
金额：
$ 8.69万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10838025
关键词：
Adolescence Adolescent Adult Aging Animal Model Attention Award Behavior Brain Child Childhood Clinical Communication Coupled Data Development Epigenetic Process Exposure to Female Foundational Skills Goals Grant Incentives Intravenous Learning Long-Term Effects Methadone Methyl-CpG-Binding Protein 2 Modeling Modification Motivation Myelin Basic Proteins Neonatal Abstinence Syndrome Neuroglia Neurons Opioid Outcome Oxycodone Paper Parents Pregnancy Publishing Rattus Reporting Research Rewards Risk Role Science Self Administration State Interests Substance Use Disorder Substance abuse problem Technical Expertise Techniques Training Woman Writing abuse liability black women career design early life adversity experience fetal opioid exposure in utero male maternal separation myelination offspring opioid exposure parent grant postnatal prenatal prenatal exposure substance use supportive environment translational model translational neuroscience white matter

项目摘要

Summary/Abstract The proposed diversity supplement for graduate trainee Chantal Aaron will provide both technical and theoretical training in animal models of substance use disorders. In alignment with the Parent Award, these studies will utilize our translational model of intravenous oxycodone self-administration (IVSA) in female rats during pregnancy. The parent grant focuses on modifications in MeCP2, an epigenetic regulator in neurons, induced by in utero exposure to oxycodone and examines effects on substance use liability in adult males and females. The studies to be performed by the candidate will use this same model of oxycodone SA during pregnancy, but will focus on different outcomes, providing her with the opportunity to develop an independent line of research during her graduate studies. Chantal will examine effects of in utero oxycodone exposure on the developmental expression of myelin basic protein (MBP), which is necessary for myelination, as clinical findings report that children born to women treated with methadone show altered white matter development in childhood. The proposed studies will also examine adolescent reward-related behaviors to determine whether changes in reward learning or incentive motivation during adolescence are impacted by prenatal oxycodone exposure. Moreover, as prenatal opioid exposure increases the risk of early adversity, these studies will include groups that experience postnatal maternal separation to model the potential exacerbation of opioid- induced effects when coupled with early adversity. The design of the proposed supplement is intended to provide the candidate with training that she can then apply to the broader field of substance use disorders, while answering important questions regarding the consequences of prenatal opioid exposure. All the techniques proposed are already well-established in the lab and the studies have been designed to ensure that the data to be collected will allow the trainee to publish at least 2 first author papers. By expanding the focus of the grant to include expression of MBP, these studies also fit with the candidates stated interest in furthering her understanding of the role of glia in development and with her prior research on myelination in cortical regions during aging. The role of glia in the long-term effects of in utero opioid exposure has been clinically implicated but has received less attention in animal models. Our aim is to provide the trainee with research experiences that will allow her to develop technical expertise while also gaining the foundational skills she will need moving forward (e.g. grant writing, science communication, networking). Importantly, this training will take place within a supportive environment, with the goal of helping Chantal establish a successful, independent career in substance abuse research.

摘要/摘要拟议的研究生学员Chantal Aaron的多样性补充剂将同时提供技术和动物使用障碍的动物模型中的理论训练。为了与父母奖一致，这些研究将利用我们在雌性大鼠中静脉内羟考酮自我给药（IVSA）的翻译模型怀孕期间。父母赠款专注于MECP2的修改，MECP2是神经元中的表观遗传调节剂，在子宫暴露于羟考酮中引起的诱导，并检查成年男性对物质使用责任的影响女性。候选人要进行的研究将在此期间使用相同的羟考酮SA模型怀孕，但会专注于不同的结果，为她提供了建立独立的机会在她的研究生学习期间的研究线。 Chantal将检查子宫羟考酮暴露对对的影响髓磷脂碱性蛋白（MBP）的发育表达，这是髓鞘的必要的，作为临床调查结果报告称，接受美沙酮治疗的妇女出生的儿童显示了变化的白质发展童年。拟议的研究还将检查青少年奖励相关的行为，以确定是否是否青春期奖励学习或激励动机的变化受到产前羟考酮的影响接触。而且，随着产前阿片类药物的暴露增加早期逆境的风险，这些研究将包括经历产后孕产妇分离以模拟阿片类药物的潜在加重的组与早期逆境相结合时诱导的影响。拟议补充的设计旨在向候选人提供培训，然后她可以将其应用于更广泛的物质使用障碍领域，同时回答有关产前阿片类药物暴露后果的重要问题。全部提出的技术已经在实验室中建立了良好的研究，并且研究旨在确保要收集的数据将允许学员至少发表2篇第一作者论文。通过扩展重点这些研究的赠款包括表达MBP，这些研究还符合候选人所列出的对进一步的兴趣她对神经胶质在发育中的作用以及先前对皮质中髓鞘的研究的理解衰老期间的区域。神经胶质在子宫阿片类药物暴露的长期作用中的作用在临床上一直是暗示但在动物模型中受到较少的关注。我们的目的是为学员提供研究可以使她发展技术专业知识的经验，同时也获得了她将获得的基础技能需要前进（例如授予写作，科学沟通，网络）。重要的是，这项培训将接受放置在支持环境中，目的是帮助Chantal建立成功，独立的药物滥用研究的职业。