Serotonin transporter expression is not sufficient to confer cytotoxicity to 3,4-methylenedioxymethamphetamine (MDMA) in vitro
Shaista Hayat, Robert J. Williams, Marcus Rattray
Journal of Psychopharmacology March 1, 2006 DOI: 10.1177/0269881106063273 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro cell study Peer reviewed |
|---|---|
| Population | Cultured COS-7 cells expressing recombinant rat SERT, human SERT-expressing JAR cells, and untransfected COS-7 cells |
| Intervention | MDMA |
| Dose | 0.1 µM–1 mM |
| Duration | 24 or 48 h exposure |
| Measures | LDH release, MTT turnover, 5-HT uptake assays |
| Topics | MDMA Serotonin |
| Key points | MDMA was cytotoxic only at 1 mM, the highest concentration tested, and this toxicity appeared in all cell lines regardless of SERT expression level. It was not blocked by the SERT inhibitors paroxetine or fluoxetine and not enhanced by forskolin, which increased 5-HT uptake capacity by 50%. The authors conclude that SERT expression is not sufficient to confer MDMA toxicity to cell lines. |
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 vivostudies 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 vitromodel 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 SERTexpressing JAR cells and to untransfected COS-7 cells which do not express SERT. Cultured cells were exposed to MDMA (0.1 µ Mñ1mM) for 24 or 48 h at 37 °C before assessing cytotoxicity by LDH release and MTT turnover. Only at the highest concentration used, 1mM, was MDMA cytotoxic, and this toxicity was found in all cell lines. Cytotoxicity caused by 48 h exposure to 1mM MDMA at 37 °C was not related to the level of SERT expression, not blocked by the SERT-blocking drugs paroxetine or .uoxetine and not enhanced, in JAR cells, by forskolin preincubation that increased 5-HT uptake capacity by 50%. We conclude that SERT expression is not suf.cient 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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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and 7 more in the library