Maternal MDMA (Ecstasy) Exposure and Fetal Physiology

这项R21探索性/开发性资助的目标是量化母体服用摇头丸（亚甲基二氧甲基苯丙胺；MDMA）对胎儿大脑和全身的影响。即使其他非法药物的使用减少（或至少保持不变），致幻性甲基苯丙胺衍生物MDMA的受欢迎程度仍在继续增加。这种MDMA趋势在青少年和年轻成人人群中尤为明显。与这一应用特别相关的是，育龄妇女和实际怀孕妇女报告的饮酒量增加。各种人类和动物研究的结果表明，怀孕期间暴露于MDMA会伤害胎儿，虽然有几个过程涉及产生这些行为异常，但胎儿对母体暴露于MDMA的实际反应尚不清楚。本提案的目的是利用子宫内技术（如近红外光谱和胎儿微透析）结合更标准的监测技术来确定胎儿对母体MDMA暴露的急性反应。实验目标：确定母体MDMA暴露对胎儿脑氧合、胎儿多巴胺能和血清素能神经传递、胎儿（和母体）心血管功能、体温、动脉血气状态和神经内分泌因素的影响；2. 将生理变化与胎儿中枢神经系统和胎儿/母亲血液中MDMA水平的变化联系起来；3、评估母体MDMA暴露后的早产儿和近产期脑组织病理学，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对注入盐水的动物的影响。模仿与一些报道的人类剂量模式一致的方案，每只母羊将三次给予2 mg/kg的MDMA治疗，每次间隔3小时，总剂量为6 mg/kg。胎儿和母亲的反应将监测到12小时后，最后一次剂量。实验目标的实现将产生大量关于MDMA对胎儿影响的新信息。这些信息将引起MDMA研究人员、临床医生和药物滥用工作者的兴趣，因为我们预计这项研究将有助于阐明怀孕期间服用MDMA的健康风险。

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.