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(+/-)-3,4-Methylenedioxymethamphetamine administration to rats does not decrease levels of the serotonin transporter protein or alter its distribution between endosomes and the plasma membrane.
J Pharmacol Exp Ther 2005; 314(3):1002-12JP

Abstract

We showed that the serotonin (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) reduces brain tissue 5-HT, decreases expression of 5-HT transporter (SERT) protein, and increases expression of glial fibrillary acidic protein (GFAP). In contrast, doses of (+/-)-3,4-methylenedioxymethamphetamine (MDMA) that decrease brain tissue 5-HT fail to alter expression of SERT or GFAP. Using a new and highly sensitive anti-SERT antibody, we determined whether MDMA alters the subcellular distribution of SERT protein by measuring SERT expression in endosomes and plasma membranes 2 weeks after MDMA administration. Rat brain tissues (caudate, cortex, and hippocampus) were collected 3 days and 2 weeks after MDMA (7.5 mg/kg i.p., every 2 h x 3 doses) or 5,7-DHT (150 microg/rat i.c.v.) administration. Representative results from cortex are as follows. At both 3 days and 2 weeks postinjection, MDMA decreased tissue 5-HT (65%) and had no effect on GFAP expression. MDMA increased heat shock protein 32 (HSP32; a marker for microglial activation) expression (30%) at 3 days, but not 2 weeks. MDMA did not alter SERT expression at either time point and did not alter SERT levels in either endosomes or plasma membranes (2 weeks). 5,7-DHT decreased tissue 5-HT (80%), increased HSP32 expression at both time points (about 50%), and increased GFAP expression at 2 weeks (40%). 5,7-DHT decreased SERT expression (33%) at 2 weeks, but not at 3 days. These findings indicate that a dosing regimen of MDMA that depletes brain 5-HT does not alter SERT protein expression or the distribution of SERT between endosomes and the plasma membrane and does not produce detectable evidence for neurotoxicity.

Authors+Show Affiliations

Clinical Psychopharmacology Section, Intramural Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15937150

Citation

Wang, Xiaoying, et al. "(+/-)-3,4-Methylenedioxymethamphetamine Administration to Rats Does Not Decrease Levels of the Serotonin Transporter Protein or Alter Its Distribution Between Endosomes and the Plasma Membrane." The Journal of Pharmacology and Experimental Therapeutics, vol. 314, no. 3, 2005, pp. 1002-12.
Wang X, Baumann MH, Xu H, et al. (+/-)-3,4-Methylenedioxymethamphetamine administration to rats does not decrease levels of the serotonin transporter protein or alter its distribution between endosomes and the plasma membrane. J Pharmacol Exp Ther. 2005;314(3):1002-12.
Wang, X., Baumann, M. H., Xu, H., Morales, M., & Rothman, R. B. (2005). (+/-)-3,4-Methylenedioxymethamphetamine administration to rats does not decrease levels of the serotonin transporter protein or alter its distribution between endosomes and the plasma membrane. The Journal of Pharmacology and Experimental Therapeutics, 314(3), pp. 1002-12.
Wang X, et al. (+/-)-3,4-Methylenedioxymethamphetamine Administration to Rats Does Not Decrease Levels of the Serotonin Transporter Protein or Alter Its Distribution Between Endosomes and the Plasma Membrane. J Pharmacol Exp Ther. 2005;314(3):1002-12. PubMed PMID: 15937150.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - (+/-)-3,4-Methylenedioxymethamphetamine administration to rats does not decrease levels of the serotonin transporter protein or alter its distribution between endosomes and the plasma membrane. AU - Wang,Xiaoying, AU - Baumann,Michael H, AU - Xu,Heng, AU - Morales,Marisela, AU - Rothman,Richard B, Y1 - 2005/06/03/ PY - 2005/6/7/pubmed PY - 2005/10/22/medline PY - 2005/6/7/entrez SP - 1002 EP - 12 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 314 IS - 3 N2 - We showed that the serotonin (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) reduces brain tissue 5-HT, decreases expression of 5-HT transporter (SERT) protein, and increases expression of glial fibrillary acidic protein (GFAP). In contrast, doses of (+/-)-3,4-methylenedioxymethamphetamine (MDMA) that decrease brain tissue 5-HT fail to alter expression of SERT or GFAP. Using a new and highly sensitive anti-SERT antibody, we determined whether MDMA alters the subcellular distribution of SERT protein by measuring SERT expression in endosomes and plasma membranes 2 weeks after MDMA administration. Rat brain tissues (caudate, cortex, and hippocampus) were collected 3 days and 2 weeks after MDMA (7.5 mg/kg i.p., every 2 h x 3 doses) or 5,7-DHT (150 microg/rat i.c.v.) administration. Representative results from cortex are as follows. At both 3 days and 2 weeks postinjection, MDMA decreased tissue 5-HT (65%) and had no effect on GFAP expression. MDMA increased heat shock protein 32 (HSP32; a marker for microglial activation) expression (30%) at 3 days, but not 2 weeks. MDMA did not alter SERT expression at either time point and did not alter SERT levels in either endosomes or plasma membranes (2 weeks). 5,7-DHT decreased tissue 5-HT (80%), increased HSP32 expression at both time points (about 50%), and increased GFAP expression at 2 weeks (40%). 5,7-DHT decreased SERT expression (33%) at 2 weeks, but not at 3 days. These findings indicate that a dosing regimen of MDMA that depletes brain 5-HT does not alter SERT protein expression or the distribution of SERT between endosomes and the plasma membrane and does not produce detectable evidence for neurotoxicity. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15937150/_+/___34_Methylenedioxymethamphetamine_administration_to_rats_does_not_decrease_levels_of_the_serotonin_transporter_protein_or_alter_its_distribution_between_endosomes_and_the_plasma_membrane_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15937150 DB - PRIME DP - Unbound Medicine ER -