Abstract
MDMA (3,4-methylenedioxymethamphetamine) causes damage to fine serotonergic fibers and apoptotic neurodegeneration in the adult rat brain. But little is known about the toxic effects of MDMA in the developing brain. The incidence of MDMA abuse is particularly high in adolescents. But the prevalence of MDMA use in woman of child-bearing age and the consequences on their offsprings are unknown. For this reason we administered MDMA (20 – 60 mg/kg) i.p. To 7-day-old rats. Rats treated with normal saline alone served as controls. Pups were sacrificed 24 hrs after injection and brain sections were examined histologically by means of De Olmos cupric silver staining to visualize degenerating cells. MDMA doses of 60 mg/kg induced significant apoptotic neurodegeneration. To explore pathogenetic mechanisms, we investigated the impact of MDMA on the neurotrophine BDNF (brain derived neurotrophic factor). Pups were sacrificed at defined time points (2, 6, 12 and 24 hrs) after injection and brains were processed for RT-PCR, real-time PCR and Western-Blot analysis. mRNA levels for BDNF were upregulated at 6 hrs in animals receiving MDMA compared to controls and even increased at 12 and 24 hours. real-time PCR analysis of the thalamus revealed similar pattern of upregulation of BDNF mRNA transcription. Determined by immunoblot protein expression of BDNF also showed an increase at 12 and 24 hours. These preliminary data suggest that a single injection of MDMA causes neurodegeneration in the neonatal rat brain and that higher doses are required for similar toxicity compared to adult rats. The upregulation in the expression of brain derived neurotrophic factor (BDNF) is may be an important mechanism that lead to survival of neuronal cells in the developing brain.
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Dzietko, M., Klaus, J., Sifringer, M. et al. 105 Mdma (ECSTASY) Causes Neurodegeneration in the Developing Rat Brain. Pediatr Res 58, 372 (2005). https://doi.org/10.1203/00006450-200508000-00134
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DOI: https://doi.org/10.1203/00006450-200508000-00134