A Novel Mouse Model of Prenatal Opioid Exposure

项目摘要/摘要 在美国，阿片类药物的使用已经达到了流行的程度，不仅对个人和他们的 家庭，还有社区。受影响最大的人群之一是孕妇及其接触过的 后代。尽管努力减少处方阿片类药物的使用，但更有效的合成类似物，如 芬太尼正变得更容易获得。芬太尼在暴露的患者中的长期影响知之甚少 孩子们。在这项建议中，我们将建立一种临床相关的小鼠模型，使其产前暴露于芬太尼。 确定暴露子代的药代动力学和功能(行为)特征。发展中 阿片类药物已知会影响特定的行为领域，我们将在早期(新生儿)和 晚年(成年)。我们假设芬太尼会减少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性。我们进一步假设这条路线和 暴露的持续时间将加剧这些缺陷。这项研究将是第一次检验 发育中的芬太尼暴露改变了短期和长期的功能结果，并将使我们 确定这些改变表型背后的关键神经回路变化，以便发育 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