PMID- 20002520 OWN - NLM STAT- MEDLINE DCOM- 20100308 LR - 20151119 IS - 1471-4159 (Electronic) IS - 0022-3042 (Linking) VI - 112 IP - 4 DP - 2010 Feb TI - Effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: implications for MDMA neurotoxicity. PG - 951-62 LID - 10.1111/j.1471-4159.2009.06515.x [doi] AB - 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. FAU - Biezonski, Dominik K AU - Biezonski DK AD - Neuroscience and Behavior Program, University of Massachusetts, Amherst, Massachusetts, USA. FAU - Meyer, Jerrold S AU - Meyer JS LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20091130 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Benzylamines) RN - 0 (Central Nervous System Stimulants) RN - 0 (Hallucinogens) RN - 0 (Neurotransmitter Uptake Inhibitors) RN - 0 (Serotonin Plasma Membrane Transport Proteins) RN - 0 (Slc18a2 protein, rat) RN - 0 (Vesicular Monoamine Transport Proteins) RN - 31363-74-3 (5,7-Dihydroxytryptamine) RN - 333DO1RDJY (Serotonin) RN - 44RAL3456C (Methamphetamine) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - PQ1P7JP5C1 (DSP 4) SB - IM MH - 5,7-Dihydroxytryptamine/pharmacology MH - Animals MH - Area Under Curve MH - Benzylamines/pharmacology MH - Brain/drug effects/metabolism/pathology MH - Central Nervous System Stimulants/administration & dosage MH - Disease Models, Animal MH - Female MH - Gene Expression/drug effects MH - Hallucinogens/*toxicity MH - Male MH - Methamphetamine/administration & dosage MH - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity MH - Neurotoxicity Syndromes/*etiology/pathology/prevention & control MH - Neurotransmitter Uptake Inhibitors/pharmacology MH - Pregnancy MH - Protein Binding/drug effects MH - Rats MH - Rats, Sprague-Dawley MH - Serotonin/metabolism MH - Serotonin Plasma Membrane Transport Proteins/*metabolism MH - Synaptosomes/drug effects/metabolism MH - Time Factors MH - Vesicular Monoamine Transport Proteins/*metabolism EDAT- 2009/12/17 06:00 MHDA- 2010/03/10 06:00 CRDT- 2009/12/17 06:00 PHST- 2009/12/17 06:00 [entrez] PHST- 2009/12/17 06:00 [pubmed] PHST- 2010/03/10 06:00 [medline] AID - JNC6515 [pii] AID - 10.1111/j.1471-4159.2009.06515.x [doi] PST - ppublish SO - J Neurochem. 2010 Feb;112(4):951-62. doi: 10.1111/j.1471-4159.2009.06515.x. Epub 2009 Nov 30.