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Biezonski DK, Meyer JS. 
“Effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: implications for MDMA neurotoxicity”. 
J Neurochem. 2010 Feb 09;112(4):951-62.
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  • Erowid RefID: 8349
  • PubMedID: 20002520
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    Abstract
    3,4-Methylenedioxymethamphetamine (MDMA; 'Ecstasy') is a popular recreational drug used worldwide. This study aimed to determine the effects of this compound on the expression of nerve terminal serotonergic markers in rats. Experiment 1 investigated MDMA-induced changes in levels of the serotonin transporter (SERT) and the vesicular monoamine transporter 2 (VMAT-2) in the hippocampus, a region with sparse dopaminergic innervation, after lesioning noradrenergic input with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). Adult male Sprague-Dawley rats were administered 100 mg/kg DSP-4 or saline 1 week prior to either an MDMA (10 mg/kg x 4) or saline binge. Two weeks following the binge treatment, the DSP-4/MDMA group unexpectedly showed little change in hippocampal VMAT-2 protein expression compared with DSP-4/Saline controls, despite large reductions in SERT levels in all regions examined in the MDMA-treated animals. Furthermore, animals treated with binge MDMA (Experiment 2) showed a striking decrease in SERT gene expression (and a lesser effect on VMAT-2) measured by quantitative RT-PCR in pooled dorsal and median raphe tissue punches, when compared with saline-treated controls. These results demonstrate that MDMA causes substantial regulatory changes in the expression of serotonergic markers, thus questioning the need to invoke distal axotomy as an explanation of MDMA-related serotonergic deficits.
    Comments and Responses to this Article
    #
    Status: display
    earth
    Jul 1, 2011 13:18
    Findings Suggest No Axonal Pruning / Neurotoxicity #
    The authors provide evidence that MDMA-induced decreases in serotonin transporter expression (commonly considered a sign of MDMA neurotoxicity) reflect adaptive changes in gene expression, not neurodegeneration.

    The final sentence of the abstract uses the phrase "distal axotomy", which refers to the type of neurotoxicity that many researchers believe MDMA causes, is the pruning or dying off of the axon of a neuron. The axon is the main transmission 'arm' of the nerve cell. This paper's findings suggest that instead of loss of axons, the cells are shifting their expression of a transporter (down regulating) in a way that previous researchers misunderstood to mean the axons were no longer present.
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