Maternal MDMA (Ecstasy) Exposure and Fetal Physiology

母体 MDMA（摇头丸）暴露与胎儿生理学

• 批准号: 6807255
• 负责人: JAMES D REYNOLDS
• 金额: $ 15.4万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6807255
• 关键词: 3,4 methylenedioxymethamphetamine; behavioral /social science research tag; body temperature; brain circulation; cardiovascular function; dopamine; drug abuse; drug metabolism; embryo /fetus; embryo /fetus toxicology; health behavior; histopathology; infrared spectrometry; maternal behavior; microdialysis; nerve injury; neuroendocrine system; neurophysiology; neurotransmitter transport; pregnancy circulation; respiratory gas level; respiratory oxygenation; serotonin; sheep

The goal of this R21 Exploratory/Development grant is to quantify the fetal cerebral and systemic effects of maternal ecstasy (methylenedioxymethamphetamine; MDMA) consumption. The popularity of the entactogenic methamphetamine derivative MDMA continues to increase even as the use of other illicit drugs decreases (or at least remain constant). This MDMA trend is particularly noticeable in adolescent and young adult populations. Of specific relevance to this application is the elevated incidence of reported consumption by women of child-bearing age and by those who are actually pregnant. Results from various human and animal studies indicate that exposure to MDMA during pregnancy can harm the fetus and while several processes have been implicated in producing these behavioral anomalies the actual responses of the fetus to maternal MDMA exposure are not known. The purpose of this proposal is to utilize in utero technologies (e.g. near-infrared spectroscopy and fetal microdialysis) in combination with more standard monitoring techniques to determine the acute fetal responses to maternal MDMA exposure. Experimental Goals: 1. To determine the effects of maternal MDMA exposure on fetal cerebral oxygenation, fetal dopaminergic and serotonergic neurotransmission, and fetal (and maternal) cardiovascular function, body temperature, arterial blood gas status, and neuroendocrine factors; 2. To relate the physiologic changes to changes in fetal CNS and fetal/maternal blood levels of MDMA; 3, To assess preterm and nearterm brain histopathology following maternal MDMA exposure and to correlate the severity (and type) of fetal neuronal injury with the observed physiologic changes. Experiments will compare the effects of MDMA exposure to saline-infused animals. Mimicking a regimen that is consistent with some reported human dosage patterns, 2 mg/kg treatments of MDMA will be thrice administered to each ewe at 3 h intervals for a total dose of 6 mg/kg. The fetal and maternal responses will monitored up to 12 h after the last dose. Achievement of the experimental goals will yield a significant amount of new information regarding the effects of MDMA upon the fetus. Such information will be of interest to MDMA researchers, clinicians, and substance-abuse workers as we anticipate that this research will help elucidate the health risks of MDMA consumption during pregnancy.

这项R21探索/开发补助金的目标是量化产妇摇头丸（亚甲二氧甲基苯丙胺; MDMA）消费对胎儿大脑和全身的影响。即使在其他非法药物使用减少（或至少保持不变）的情况下，致内陷性甲基苯丙胺衍生物亚甲二氧基甲基安非他明的流行程度仍在继续增加。这种MDMA趋势在青少年和年轻成年人中尤其明显。与这一应用特别相关的是，据报告育龄妇女和实际怀孕妇女消费大麻的情况有所增加。各种人类和动物研究的结果表明，怀孕期间接触MDMA会伤害胎儿，虽然有几个过程与产生这些行为异常有关，但胎儿对母体接触MDMA的实际反应尚不清楚。本提案的目的是利用宫内技术（例如近红外光谱和胎儿微透析）结合更标准的监测技术，以确定胎儿对母体MDMA暴露的急性反应。 实验目标：1.确定母亲MDMA暴露对胎儿脑氧合、胎儿多巴胺能和多巴胺能神经传递、胎儿（和母亲）心血管功能、体温、动脉血气状态和神经内分泌因子的影响; 2.将生理变化与胎儿CNS和胎儿/母体血液中MDMA水平的变化联系起来; 3，评估母体MDMA暴露后早产和近足月脑组织病理学，并将胎儿神经元损伤的严重程度（和类型）与观察到的生理变化联系起来。实验将比较MDMA暴露于盐水输注动物的影响。模仿与一些报告的人类剂量模式一致的方案，每只母羊以3 h间隔给予3次2 mg/kg MDMA治疗，总剂量为6 mg/kg。末次给药后12小时内监测胎儿和母体反应。实验目标的实现将产生大量关于MDMA对胎儿影响的新信息。这些信息将是MDMA研究人员，临床医生和药物滥用工作者感兴趣的，因为我们预计这项研究将有助于阐明怀孕期间MDMA消费的健康风险。