Won L, Bubula N, Heller A (2002) Fetal exposure to (+/-)-methylenedioxymethamphetamine in utero enhances the development and metabolism of serotonergic neurons in three-dimensional reaggregate tissue culture. Brain Res Dev Brain Res 137: 67-73.
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The effects of maternal exposure to MDMA on fetal brain development were investigated in mice via three-dimensional reaggregrate tissue culture systems made from fetal mouse mesencephalic tegmentum, a region containing developing serotonergic and dopaminergic neurons. Pregnant mice (dams) were given a regimen of 40 mg/kg MDMA twice a day for 7 days (from gestational day 6 through 13). Dams were killed on gestational day 14, and monoamine content of striatum was examined via HPLC. Embryos were also harvested, and mesencephalic tegmentum selected for the reaggregate tissue culture. After 18 days in culture, reaggregation procedures were carried out. On culture days 22 and 36, culture media was analyzed for 5-HT, DA and metabolites. Pregnant mice receiving MDMA gained less weight than pregnant mice receiving saline, and striatal homovanillic acid (HVA, metabolite of DA) was higher in MDMA-treated dams. However, there was no sign of reduced dopamine content, a surprising finding given the regimen used. Reaggregated cultures from MDMA-treated dams had elevated 5-HT and 5-HIAA on culture day 22 and 36. Media also showed elevated DOPAC (DA metabolite) on both days 22 and 36 without finding any changes in DA itself, when compared with media from aggregates from saline-treated dams. In mice, fetal exposure seems to enhance activity of developing serotonergic and dopaminergic neurons (particularly serotonergic neurons). The authors state that findings of enhanced function for fetal serotonergic and dopaminergic neurons also occurs after mice are exposed to nicotine, cocaine and methamphetamine. It is difficult to determine what these findings indicate about use of ecstasy during pregnancy, as MDMA neurotoxicity affects dopaminergic neurons, and not serotonergic neurons, in mice. Since there were differences in weight gain between saline-treated and MDMA-treated dams, changes in development due to changes in maternal weight or feeding habits cannot be ruled out. Overall, this study adds to the series of inconclusive or contradictory findings concerning the effects of MDMA on mammal development, including another recently located paper (Meyer et al. 2002).

 
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