Consequences of fentanyl self-administration during pregnancy

摘要 对孕妇或一般育龄妇女滥用阿片类药物是一个紧迫的公共卫生问题。 在过去的几年里，在分娩和分娩时使用阿片类药物的妇女人数增加了四倍多 十年。而怀孕期间使用阿片类药物的直接影响，即新生儿阿片类药物的戒断 关于阿片类药物滥用的长期有害影响，人们只有有限的认识 在怀孕期间对发育中的孩子的影响。本提案旨在研究产前使用芬太尼的效果 暴露及其对后代的短期和长期影响--从婴儿期到成年期--使用 一种翻译相关的方法，在这种方法中，大鼠在延长的时间内静脉注射芬太尼。 在怀孕前和整个怀孕期间的接触条件。在一个特定的目标中，我们将测试每天 扩大静脉注射芬太尼自我给药的途径构成了一个翻译相关的模型 对孕妇滥用芬太尼，导致新生儿阿片类药物戒断，损害后代发育， 并改变了对鸦片类药物的敏感度，这种敏感度会一直持续到成年。 我们将全面评估新生儿阿片类药物戒断的总体健康状况、发生情况和严重程度。 子代达到与年龄相适应的身体和行为发育里程碑，随后 评估对阿片类药物的敏感性。与来自带枷锁的盐水控制大坝的幼崽相比，我们预计 产前暴露芬太尼会导致发育里程碑的延迟实现，并增加 对芬太尼的敏感性，我们预计缺陷的严重程度将直接与芬太尼的暴露水平有关。 此外，我们预计，通过芬太尼和芬太尼之间的交叉培养来改善产妇护理 和盐碱化水坝，将改善观察到的发展效果。拟议研究的结果将 提供有关芬太尼暴露本身的作用、阿片类药物的存在/严重程度等所需信息 暴露在铅暴露下的幼鼠持续性身体和行为损害的戒断和母婴护理改变 芬太尼。最终，我们的研究应该带来对识别治疗至关重要的知识。 机会，包括产前和产后。

ABSTRACT Opioid abuse of pregnant women or women of childbearing age in general is an urgent public health concern. The number of women using opioids presenting at labor and delivery has more than quadrupled in the last decade. While the imminent effects of opioid use during pregnancy, namely neonatal opiate withdrawal syndrome, are well described, there is only limited knowledge about the long-term harmful effect of opioid abuse during pregnancy on the developing child. This proposal aims to investigate the effects of prenatal fentanyl exposure, and its short- and long-term consequences on the offspring – from infancy through adulthood- using a translationally relevant approach in which rat dams self-administer fentanyl intravenously under extended- access conditions prior and throughout pregnancy. In one specific Aim we will test the hypothesis that daily extended-access to intravenous fentanyl self-administration constitutes a translationally relevant model of fentanyl abuse on pregnant women, that induces neonatal opioid withdrawal, impaired offspring development, and altered sensitivity to opiates that persists throughout adulthood. We will assess comprehensively the overall health, occurrence and severity of neonatal opiate withdrawal and achievement of age-appropriate somatic and behavioral developmental milestones by the offspring, followed by evaluation of sensitivity to opiates. In comparison to pups from yoked saline control dams, we expect that prenatal fentanyl exposure will lead to delayed achievement of developmental milestones, and increased sensitivity to fentanyl, and we expect the severity of deficits will be directly related to level of fentanyl exposure. In addition, we expect that improved maternal care, as achieved by cross-fostering of litters between fentanyl and saline dams, will ameliorate the observed developmental effects. The results from the proposed studies will provide needed information regarding the role of fentanyl exposure itself, the presence/severity of opioid withdrawal and altered maternal care in the persistent physical and behavioral impairment of pups exposed to fentanyl. Ultimately, our studies should lead to knowledge that is vital for the identification of treatment opportunities, both pre- and postpartum.