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.

该R21探索/开发赠款的目的是量化孕产妇摇头丸（甲基二甲基甲基苯丙胺； MDMA）消耗的胎儿脑和系统作用。即使使用其他非法药物降低（或至少保持恒定），即使使用其他非法药物的使用，无甲基苯丙胺衍生物MDMA的普及仍在增加。在青少年和成年人的年轻人中，这种MDMA趋势尤其明显。与此应用的具体相关性是，育龄妇女和实际怀孕的妇女报告的消费量的发病率升高。各种人类和动物研究的结果表明，怀孕期间对MDMA的暴露会损害胎儿，尽管几个过程与产生这些行为异常有关，但尚不清楚胎儿对母体MDMA暴露的实际反应。该提案的目的是在子宫技术（例如近红外光谱和胎儿微透析）中使用与更多标准监测技术结合使用，以确定对母体MDMA暴露的急性胎儿反应。 实验目标：1。确定母体MDMA暴露对胎儿大脑氧合，胎儿多巴胺能和血清素能神经传递以及胎儿（以及母体）心血管功能，体温，动脉血液气体状况以及神经内分泌因子的影响； 2。将生理变化与胎儿中枢神经系统的变化以及MDMA的胎儿/母体血液水平相关联； 3，评估母体MDMA暴露后的早产和近期脑组织病理学，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相关联。实验将比较MDMA暴露于盐水注入盐水的动物的影响。模仿与一些报道的人剂量模式一致的治疗方案，将以3小时的间隔对每种母羊的MDMA处理2 mg/kg治疗，总剂量为6 mg/kg。上次剂量后，胎儿和母体反应将在12小时内进行监测。实验目标的实现将产生有关MDMA对胎儿影响的大量新信息。 MDMA研究人员，临床医生和药物滥用工人将感兴趣，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。