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Short- and long-term effects of MDMA (“ecstasy”) on synaptosomal and vesicular uptake of neurotr

Short- and long-term effects of MDMA (“ecstasy”) on synaptosomal and vesicular uptake of neurotr

  1. BitterSweet
    Inger Lise Bogen, Kristin Huse Haug, Oddvar Myhre, Frode Fonnum, Short- and long-term effects of MDMA (“ecstasy”) on synaptosomal and vesicular uptake of neurotransmitters in vitro and ex vivo, Neurochemistry International, Volume 43, Issues 4–5, September–October 2003, Pages 393-400, ISSN 0197-0186, http://dx.doi.org/10.1016/S0197-0186(03)00027-5.
    (http://www.sciencedirect.com/science/article/pii/S0197018603000275)

    Abstract
    3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a commonly abused drug which has been shown to be neurotoxic to serotonergic neurons in many species. The exact mechanism responsible for the neurotoxicity of MDMA is, however, poorly understood. In this study, the effects of MDMA on the synaptosomal and vesicular uptake of neurotransmitters were investigated. Our results show that MDMA (0.5–20 μM) reduces both synaptosomal and vesicular uptake of serotonin and dopamine in a dose dependent manner in vitro, while the uptake of glutamate and γ-aminobutyric acid (GABA) remains unaffected. Ex vivo experiments support the importance of the monoamines, with predominant dopaminergic inhibition at short-term exposure (3 × 15 mg/kg; 2-h intervals), and exclusively serotonergic inhibition at long-term exposure (2 × 10 mg/kg per day; 4 days). This study also compares MDMA and the structurally related antidepressant paroxetine, in an attempt to reveal possible cellular mechanisms for the serotonergic toxicity of MDMA. One important difference between paroxetine and MDMA is that only MDMA has the capability of inhibiting vesicular uptake of monoamines at doses used. We suggest that inhibition of the vesicular monoamine transporter-2, and a following increase in cytoplasmatic monoamine concentrations, might be crucial for the neurotoxic effect of MDMA.
    Keywords: 3,4-Methylenedioxymethamphetamine; Paroxetine; Synaptosomes; Synaptic vesicles; Uptake; Monoamines; Serotonin; Dopamine