A Novel Mouse Model of Prenatal Opioid Exposure

项目总结/摘要 美国境内的阿片类药物使用已达到流行病的程度，不仅对个人及其家庭产生了负面影响， 家庭，还有社区。受影响最严重的人群之一是孕妇及其接触者。 后代尽管努力减少处方阿片类药物的获得，但更有效的合成类似物，如 芬太尼变得越来越容易获得。很少有人知道芬太尼的长期影响， 孩子在这项提议中，我们将开发一种临床相关的产前芬太尼暴露小鼠模型， 确定暴露后代的药代动力学和功能（行为）特征。发育 已知阿片类药物会影响特定的行为领域，我们将在早期（新生儿）和 成年人（Adult）我们假设芬太尼会降低与药物奖励相关的行为表现 以及成瘾、认知、情感、社会结果和运动协调。我们进一步指出，路线和 暴露的持续时间将加剧这些缺陷。这项研究将是第一个研究如何长期 发展芬太尼暴露改变短期和长期的功能结果，并将使我们能够 确定这些改变的表型背后的关键神经回路变化，以发展 暴露儿童的治疗方法

PROJECT SUMMARY/ABSTRACT Opioid use within the US has reached epidemic proportions, negatively impacting not just individuals and their families, but also communities. One of the most affected populations is pregnant women and their exposed offspring. Despite efforts to reduce access to prescription opioids, more potent, synthetic analogs such as fentanyl are becoming more readily available. Little is known of the long-term effects of fentanyl in exposed children. In this proposal, we will develop a clinically relevant mouse model of prenatal fentanyl exposure to determine the pharmacokinetic and functional (behavioral) profiles in exposed offspring. Developmental opioids are known to affect specific behavioral domains, and we will test offspring at both early (neonatal) and late (adult) ages. We hypothesize that fentanyl will diminish performance of behaviors related to drug reward and addiction, cognition, affect, social outcomes, and motor coordination. We further posit that the route and duration of exposure will exacerbate these deficiencies. This study will be the first to examine how long-term developmental fentanyl exposure alters both short- and long-term functional outcomes and will position us to determine the critical neural circuit changes underlying these altered phenotypes in order to develop therapeutic approaches in exposed children