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.
