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Serotonin transporter expression is not sufficient to confer cytotoxicity to 3,4-methylenedioxymethamphetamine (MDMA) in vitro.
J Psychopharmacol. 2006 Mar; 20(2):257-63.JP

Abstract

There is much evidence from animal studies that the recreational drug MDMA is a selective toxin which damages serotonin nerve terminals and axons. These in vivo studies show that an interaction between MDMA and the serotonin transporter protein (SERT) is the .rst step in toxicity. To further our understanding of the biochemical processes of MDMA toxicity we wished to use an in vitro model for toxicity. We produced two COS-7 cell lines with different levels of expression of recombinant rat SERT, as determined by 5-HT uptake assays, and compared them to human SERT expressing JAR cells and to untransfected COS-7 cells which do not express SERT. Cultured cells were exposed to MDMA (0.1 microM-1 mM) for 24 or 48 h at 37 degrees C before assessing cytotoxicity by LDH release and MTT turnover. Only at the highest concentration used, 1 mM, was MDMA cytotoxic, and this toxicity was found in all cell lines. Cytotoxicity caused by 48 h exposure to 1 mM MDMA at 37 degrees C was not related to the level of SERT expression, not blocked by the SERT-blocking drugs paroxetine or fluoxetine and not enhanced, in JAR cells, by forskolin preincubation that increased 5-HT uptake capacity by 50%. We conclude that SERT expression is not sufficient to confer MDMA toxicity to cell lines. Therefore SERT-expressing cell lines do not offer a simple model system to elucidate the mechanisms underlying MDMA toxicity.

Authors+Show Affiliations

Laboratory of Molecular Signalling, The Babraham Institute, Cambridge, UK.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16510483

Citation

Hayat, Shaista, et al. "Serotonin Transporter Expression Is Not Sufficient to Confer Cytotoxicity to 3,4-methylenedioxymethamphetamine (MDMA) in Vitro." Journal of Psychopharmacology (Oxford, England), vol. 20, no. 2, 2006, pp. 257-63.
Hayat S, Williams RJ, Rattray M. Serotonin transporter expression is not sufficient to confer cytotoxicity to 3,4-methylenedioxymethamphetamine (MDMA) in vitro. J Psychopharmacol (Oxford). 2006;20(2):257-63.
Hayat, S., Williams, R. J., & Rattray, M. (2006). Serotonin transporter expression is not sufficient to confer cytotoxicity to 3,4-methylenedioxymethamphetamine (MDMA) in vitro. Journal of Psychopharmacology (Oxford, England), 20(2), 257-63.
Hayat S, Williams RJ, Rattray M. Serotonin Transporter Expression Is Not Sufficient to Confer Cytotoxicity to 3,4-methylenedioxymethamphetamine (MDMA) in Vitro. J Psychopharmacol (Oxford). 2006;20(2):257-63. PubMed PMID: 16510483.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serotonin transporter expression is not sufficient to confer cytotoxicity to 3,4-methylenedioxymethamphetamine (MDMA) in vitro. AU - Hayat,Shaista, AU - Williams,Robert J, AU - Rattray,Marcus, PY - 2006/3/3/pubmed PY - 2006/8/10/medline PY - 2006/3/3/entrez SP - 257 EP - 63 JF - Journal of psychopharmacology (Oxford, England) JO - J. Psychopharmacol. (Oxford) VL - 20 IS - 2 N2 - There is much evidence from animal studies that the recreational drug MDMA is a selective toxin which damages serotonin nerve terminals and axons. These in vivo studies show that an interaction between MDMA and the serotonin transporter protein (SERT) is the .rst step in toxicity. To further our understanding of the biochemical processes of MDMA toxicity we wished to use an in vitro model for toxicity. We produced two COS-7 cell lines with different levels of expression of recombinant rat SERT, as determined by 5-HT uptake assays, and compared them to human SERT expressing JAR cells and to untransfected COS-7 cells which do not express SERT. Cultured cells were exposed to MDMA (0.1 microM-1 mM) for 24 or 48 h at 37 degrees C before assessing cytotoxicity by LDH release and MTT turnover. Only at the highest concentration used, 1 mM, was MDMA cytotoxic, and this toxicity was found in all cell lines. Cytotoxicity caused by 48 h exposure to 1 mM MDMA at 37 degrees C was not related to the level of SERT expression, not blocked by the SERT-blocking drugs paroxetine or fluoxetine and not enhanced, in JAR cells, by forskolin preincubation that increased 5-HT uptake capacity by 50%. We conclude that SERT expression is not sufficient to confer MDMA toxicity to cell lines. Therefore SERT-expressing cell lines do not offer a simple model system to elucidate the mechanisms underlying MDMA toxicity. SN - 0269-8811 UR - https://www.unboundmedicine.com/medline/citation/16510483/Serotonin_transporter_expression_is_not_sufficient_to_confer_cytotoxicity_to_34_methylenedioxymethamphetamine__MDMA__in_vitro_ L2 - http://journals.sagepub.com/doi/full/10.1177/0269881106063273?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -