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Consequences of fentanyl self-administration during pregnancy

怀孕期间自行服用芬太尼的后果

基本信息

批准号：
10373001
负责人：
Daniela Rüedi-Bettschen
金额：
$ 19.38万
依托单位：
UNIVERSITY OF MISSISSIPPI MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10373001
关键词：
Achievement Adult Adult Children Age Analgesics Behavior Behavioral Birth Caring Child Consensus Development Dose Drug Exposure Elements Emotional Environment Evaluation Exposure to Female of child bearing age Fentanyl Fetus Fostering Future Health Human Impairment Individual Injections Intake Intravenous Investigation Knowledge Lead Long-Term Effects Longevity Low Birth Weight Infant Maternal Behavior Modeling Neonatal Neonatal Abstinence Syndrome Opioid Outcome Overdose Pain Patients Personal Satisfaction Pharmaceutical Preparations Postpartum Period Pregnancy Pregnancy Complications Pregnant Women Premature Birth Protocols documentation Public Health Rattus Research Personnel Risk Rodent Role Saline Self Administration Severities Substance Withdrawal Syndrome Testing Time Weight Withdrawal Woman adolescent offspring behavioral impairment delivery complications effective intervention experimental group experimental study fentanyl abuse fetal opioid exposure improved in utero infancy interest neonatal exposure offspring opioid abuse opioid exposure opioid use opioid use disorder opioid withdrawal perinatal period postnatal preclinical study pregnant prenatal prenatal exposure pup respiratory success treatment strategy

项目摘要

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.

摘要孕妇或一般育龄妇女滥用类阿片是一个紧迫的公共卫生问题。去年，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。十年虽然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戒断，综合征，有很好的描述，只有有限的知识阿片类药物滥用的长期有害影响对发育中的孩子的影响。该提案旨在调查产前芬太尼的影响暴露，及其对后代的短期和长期后果-从婴儿期到成年期-使用一种预防相关的方法，其中大鼠母鼠在延长- 怀孕前和怀孕期间的准入条件。在一个特定的目标，我们将测试的假设，每天静脉内芬太尼自我给药的扩展途径构成了一种预防性相关模型，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，以及对阿片类药物的敏感性改变，这种改变会持续到整个成年期。我们将全面评估新生儿阿片类药物戒断的整体健康状况、发生率和严重程度，后代达到与年龄相适应的身体和行为发育里程碑，对阿片类药物敏感性的评估。与来自轭式盐水对照母鼠的幼仔相比，我们预计，产前芬太尼暴露将导致发育里程碑的延迟实现，对芬太尼的敏感性，我们预计缺陷的严重程度将与芬太尼暴露水平直接相关。此外，我们预计，通过芬太尼和芬太尼之间的交叉寄养，和盐水坝，将改善观察到的发育影响。拟议研究的结果将提供关于芬太尼暴露本身的作用、阿片类药物的存在/严重程度的必要信息在暴露于以下物质的幼仔的持续身体和行为损伤中的戒断和改变的母体护理芬太尼最终，我们的研究应该导致知识，这是至关重要的确定治疗机会，包括产前和产后。