MDMA administration to pregnant Sprague–Dawley rats results in its passage to the fetal compartment

Recent investigations have demonstrated that prenatal 3,4-methylenedeoxymethamphetamine (MDMA; ecstasy) exposure in rats results in significant and persistent changes in the developing brain. However, no published pharmacokinetic studies exist demonstrating that MDMA administered during pregnancy passes to the fetal compartment. This leaves open the question whether MDMA is directly acting on the fetal brain to produce the observed changes in previous studies, or whether such effects are an indirect result of MDMA administration to the pregnant dam. Therefore, pregnant rats were administered a single dose of MDMA (15 mg/kg, subcutaneous) at embryonic day 14 (E14) and the levels of MDMA and its metabolite 3,4-methylenedioxyamphetamine (MDA) were quantified in maternal plasma, amniotic fluid, and fetal brain over 8 h by HPLC. The time course of MDMA and MDA metabolism was reliable and reproducible in all tissues. There was a strong correlation between fetal amniotic fluid and fetal brain suggesting that amniotic fluid could be used to reliably estimate fetal brain levels without directly utilizing fetal brain tissue. These data also provide a framework for subsequent in vitro cell culture studies using biologically relevant MDMA doses.