PMID- 20298763 OWN - NLM STAT- MEDLINE DCOM- 20100820 LR - 20131121 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 168 IP - 1 DP - 2010 Jun 16 TI - MDMA causes a redistribution of serotonin transporter from the cell surface to the intracellular compartment by a mechanism independent of phospho-p38-mitogen activated protein kinase activation. PG - 82-95 LID - 10.1016/j.neuroscience.2010.03.018 [doi] AB - 3,4-methylenedioxymethamphetamine (MDMA) causes long-term serotonin depletion and reduced serotonin transporter (SERT) function in humans and in animal models. Using quantitative Western blotting and real-time PCR, we have shown that total SERT protein in the striatum and nucleus accumbens and mRNA levels in the dorsal raphe nucleus were not significantly changed following MDMA exposure in rats (4 x 2 h i.p. injections, 10 mg/kg each). In mouse neuroblastoma (N(2)A) cells transiently expressing green fluorescent protein-tagged human SERT (GFP-hSERT), we have shown redistribution of SERT from the cell surface to intracellular vesicles on exposure to MDMA using cell surface biotinylation, total internal reflection fluorescence microscopy (TIRFM) and live-cell confocal microscopy. To investigate the mechanism responsible for SERT redistribution, we used specific antibodies to phospho-p38-mitogen activated protein kinase (p38 MAPK), a known signalling pathway involved in SERT membrane expression. We found that p38 MAPK activation was not involved in the MDMA-induced redistribution of SERT from the cell-surface to the cell interior. A loss of SERT from the cell surface on acute exposure to MDMA may contribute to the decreased SERT function seen in rats exposed to MDMA. CI - 2010 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Kivell, B AU - Kivell B AD - School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, Wellington, New Zealand. bronwyn.kivell@vuw.ac.nz FAU - Day, D AU - Day D FAU - Bosch, P AU - Bosch P FAU - Schenk, S AU - Schenk S FAU - Miller, J AU - Miller J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100315 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Serotonin Plasma Membrane Transport Proteins) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Animals MH - Blotting, Western MH - Brain/drug effects/metabolism MH - Cell Line, Tumor MH - Cell Membrane/metabolism MH - Enzyme Activation MH - Male MH - Mice MH - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity MH - Phosphorylation MH - Protein Transport MH - Rats MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction MH - Serotonin Plasma Membrane Transport Proteins/*metabolism MH - p38 Mitogen-Activated Protein Kinases/*metabolism EDAT- 2010/03/20 06:00 MHDA- 2010/08/21 06:00 CRDT- 2010/03/20 06:00 PHST- 2009/11/11 00:00 [received] PHST- 2010/03/08 00:00 [revised] PHST- 2010/03/09 00:00 [accepted] PHST- 2010/03/20 06:00 [entrez] PHST- 2010/03/20 06:00 [pubmed] PHST- 2010/08/21 06:00 [medline] AID - S0306-4522(10)00369-6 [pii] AID - 10.1016/j.neuroscience.2010.03.018 [doi] PST - ppublish SO - Neuroscience. 2010 Jun 16;168(1):82-95. doi: 10.1016/j.neuroscience.2010.03.018. Epub 2010 Mar 15.