PMID:20002520

Citation	Biezonski, DK and Meyer, JS (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. J. Neurochem. 112:951-62
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.
Links	PubMed Online version:10.1111/j.1471-4159.2009.06515.x
Keywords	5,7-Dihydroxytryptamine/pharmacology; Animals; Area Under Curve; Benzylamines/pharmacology; Brain/drug effects; Brain/metabolism; Brain/pathology; Central Nervous System Stimulants/administration & dosage; Disease Models, Animal; Female; Gene Expression/drug effects; Hallucinogens/toxicity; Male; Methamphetamine/administration & dosage; N-Methyl-3,4-methylenedioxyamphetamine/toxicity; Neurotoxicity Syndromes/etiology; Neurotoxicity Syndromes/pathology; Neurotoxicity Syndromes/prevention & control; Neurotransmitter Uptake Inhibitors/pharmacology; Pregnancy; Protein Binding/drug effects; Rats; Rats, Sprague-Dawley; Serotonin/metabolism; Serotonin Plasma Membrane Transport Proteins/metabolism; Synaptosomes/drug effects; Synaptosomes/metabolism; Time Factors; Vesicular Monoamine Transport Proteins/metabolism
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:SC6A4	involved_in	GO:0010033: response to organic substance	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.