Oxycodone Neonatal Opioid Withdrawal Syndrome and Adult Abuse Liability

摘要/摘要 拟议为毕业实习生Chantal Aaron提供的多样性补助金将提供技术和 物质使用障碍动物模型的理论训练。为了与家长奖保持一致，这些 研究将利用我们的雌性大鼠静脉注射羟考酮自我给药(IVSA)的翻译模型 在怀孕期间。父母拨款的重点是对MeCP2的修饰，MeCP2是神经元的表观遗传调节因子， 由宫内接触羟考酮引起的，并检查对成年男性和 女性。候选人将进行的研究将使用同样的羟考酮SA模型 怀孕，但会关注不同的结局，为她提供了发展独立的机会 在她的研究生学习期间，她的研究方向。Chantal将研究宫内羟考酮暴露对 髓鞘形成所必需的髓鞘碱性蛋白(MBP)的临床发育表达 研究结果表明，接受美沙酮治疗的妇女所生的孩子在 童年。拟议的研究还将检查青少年与奖励相关的行为，以确定 青春期奖赏学习或激励动机的变化受产前羟考酮的影响 曝光。此外，由于产前阿片类药物暴露增加了早期逆境的风险，这些研究将 包括经历产后母体分离的小组，以模拟阿片类药物的潜在恶化- 当与早期的逆境相结合时，会产生影响。拟议补编的设计意在 为应聘者提供培训，然后她可以应用于更广泛的药物使用障碍领域， 同时回答有关产前阿片类药物暴露后果的重要问题。所有的 提出的技术已经在实验室中得到了很好的证实，研究的设计也是为了确保 收集的数据将允许学员发表至少2篇第一作者论文。通过扩大 拨款包括MBP的表达，这些研究也符合候选人声明的进一步兴趣 她对胶质细胞在发育中的作用的理解，以及她之前对皮质髓鞘形成的研究 在老龄化过程中的区域。神经胶质细胞在阿片类药物宫内暴露的长期影响中的作用已经在临床上得到了证实。 有牵连，但在动物模型中受到的关注较少。我们的目标是为学员提供研究 这些经验将使她在发展技术专长的同时获得她将获得的基础技能 需要向前推进(例如，拨款申请、科学交流、联网)。重要的是，这次培训将需要 在一个支持性的环境中，目标是帮助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.