Effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: implications for MDMA neurotoxicity

• Published in: Journal of neurochemistry 2010-02, Vol.112 (4), p.951-962
• Main Authors: Biezonski, Dominik K, Meyer, Jerrold S
• Format: Article
• Language: English
• Subjects: 3,4-methylenedioxymethamphetamine; 5,7-Dihydroxytryptamine - pharmacology; Animals; Area Under Curve; Benzylamines - pharmacology; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain - pathology; Cell division; Cell physiology; Central Nervous System Stimulants - administration & dosage; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression - drug effects; Hallucinogens - toxicity; Male; Medical sciences; Membrane and intracellular transports; Methamphetamine; Methamphetamine - administration & dosage; Molecular and cellular biology; N-Methyl-3,4-methylenedioxyamphetamine - toxicity; neurodegeneration; Neurology; Neurotoxicity; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - pathology; Neurotoxicity Syndromes - prevention & control; Neurotransmitter Uptake Inhibitors - pharmacology; Pregnancy; Protein Binding - drug effects; Proteins; Rats; Rats, Sprague-Dawley; Rodents; serotonin; Serotonin - metabolism; Serotonin Plasma Membrane Transport Proteins - metabolism; serotonin transporter; Synaptosomes - drug effects; Synaptosomes - metabolism; Time Factors; Vesicular Monoamine Transport Proteins - metabolism; vesicular monoamine transporter 2
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.06515.x

J. Neurochem. (2009) 112, 951-962. 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.