Oxycodone Neonatal Opioid Withdrawal Syndrome and Adult Abuse Liability

总结/摘要 为毕业实习生Chantal Aaron提出的多样性补充将提供技术和 物质使用障碍动物模型的理论培训。与家长奖一致，这些 研究将利用我们的雌性大鼠静脉内羟考酮自我给药（IVSA）转化模型 孕期父母资助的重点是MeCP 2的修饰，MeCP 2是神经元中的表观遗传调节因子， 子宫内暴露于羟考酮引起的，并检查对成年男性物质使用倾向的影响， 女性候选人进行的研究将使用相同型号的羟考酮SA， 怀孕，但将侧重于不同的结果，为她提供发展独立的机会， 研究生学习期间的研究方向。Chantal将检查子宫内羟考酮暴露对 髓鞘形成所必需的髓鞘碱性蛋白（MBP）的发育表达， 研究结果报告说，用美沙酮治疗的妇女所生的孩子显示出白色发育的改变， 童年.拟议中的研究还将检查青少年与奖励有关的行为，以确定是否 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 exposure.此外，由于产前阿片类药物暴露会增加早期逆境的风险，这些研究将 包括经历产后母亲分离的群体，以模拟阿片样物质的潜在加重， 与早期逆境相结合的诱导效应。拟议补编的设计旨在 为候选人提供培训，使其能够应用于更广泛的物质使用障碍领域， 同时回答关于产前阿片类药物暴露后果的重要问题。所有的 提出的技术已经在实验室中得到了很好的建立，研究的目的是确保 所收集的数据将允许受训者发表至少2篇第一作者论文。通过扩大重点， 补助金包括MBP的表达，这些研究也符合候选人表示有兴趣进一步 她对神经胶质细胞在发育中的作用的理解，以及她之前对皮层髓鞘形成的研究， 区域老化。神经胶质细胞在子宫内阿片类药物暴露的长期影响中的作用已在临床上得到证实。 但在动物模型中受到的关注较少。我们的目标是为受训者提供研究 这些经验将使她能够发展技术专长，同时获得她将获得的基础技能。 需要向前推进（例如，撰写赠款、科学交流、建立网络）。重要的是，这项培训将 在一个支持性的环境中，帮助Chantal建立一个成功的，独立的 从事药物滥用研究

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.