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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; 112(4):951-62JN

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.

Authors+Show Affiliations

Neuroscience and Behavior Program, University of Massachusetts, Amherst, Massachusetts, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

20002520

Citation

Biezonski, Dominik K., and Jerrold S. Meyer. "Effects of 3,4-methylenedioxymethamphetamine (MDMA) On Serotonin Transporter and Vesicular Monoamine Transporter 2 Protein and Gene Expression in Rats: Implications for MDMA Neurotoxicity." Journal of Neurochemistry, vol. 112, no. 4, 2010, pp. 951-62.
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;112(4):951-62.
Biezonski, D. K., & Meyer, J. S. (2010). Effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: implications for MDMA neurotoxicity. Journal of Neurochemistry, 112(4), pp. 951-62. doi:10.1111/j.1471-4159.2009.06515.x.
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;112(4):951-62. PubMed PMID: 20002520.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: implications for MDMA neurotoxicity. AU - Biezonski,Dominik K, AU - Meyer,Jerrold S, Y1 - 2009/11/30/ PY - 2009/12/17/entrez PY - 2009/12/17/pubmed PY - 2010/3/10/medline SP - 951 EP - 62 JF - Journal of neurochemistry JO - J. Neurochem. VL - 112 IS - 4 N2 - 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. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/20002520/Effects_of_34_methylenedioxymethamphetamine__MDMA__on_serotonin_transporter_and_vesicular_monoamine_transporter_2_protein_and_gene_expression_in_rats:_implications_for_MDMA_neurotoxicity_ L2 - https://doi.org/10.1111/j.1471-4159.2009.06515.x DB - PRIME DP - Unbound Medicine ER -