Oxycodone Neonatal Opioid Withdrawal Syndrome and Adult Abuse Liability

点击翻译按钮获取中文摘要

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.