Non-Serotonergic Neurotoxicity by MDMA (Ecstasy) in Neurons Derived from Mouse P19 Embryonal Carcinoma Cells.
Dina Popova, Andréas Forsblad, Sanaz Hashemian, Stig O P Jacobsson
PLoS One November 18, 2016 DOI: 10.1371/journal.pone.0166750 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro cell study Peer reviewed |
|---|---|
| Population | Neuronally differentiated P19 mouse embryonal carcinoma cells |
| Interventions | MDMA clorgyline deprenyl fluoxetine N-acetylcysteine |
| Measures | MTT reduction assay, LDH activity assay, mitochondrial membrane potential (ΔΨm) |
| Topics | MDMA Serotonin |
| Keywords | Neurons Cell line, tumor Animals Mice N-methyl-3,4-methylenedioxyamphetamine Selegiline Clorgyline Fluoxetine Monoamine oxidase Cell differentiation Cell survival Gene expression Membrane potential, mitochondrial |
| Key points | MDMA produced concentration-, time-, and temperature-dependent toxicity in differentiated P19 mouse neurons. The authors report that this toxicity was not mimicked or blocked by MAO inhibitors (clorgyline, deprenyl) or the SERT inhibitor fluoxetine, not prevented by antioxidants (alpha-tocopherol, N-acetylcysteine), and not accompanied by changes in mitochondrial membrane potential, suggesting the mechanism does not involve the serotonergic system, oxidative stress, or mitochondrial dysfunction. |
Abstract
3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differentiated P19 neurons, as measured by intracellular MTT reduction and extracellular LDH activity assays. The P19-derived neurons express both the serotonin reuptake transporter (SERT), that is functionally active, and the serotonin metabolizing enzyme monoamine oxidase A (MAO-A). The involvement of these proteins in the MDMA-induced toxicity was investigated by a pharmacological approach. The MAO inhibitors clorgyline and deprenyl, and the SERT inhibitor fluoxetine, per se or in combination, were not able to mimic the toxic effects of MDMA in the P19-derived neurons or block the MDMA-induced cell toxicity. Oxidative stress has been implicated in MDMA-induced neurotoxicity, but pre-treatment with the antioxidants α-tocopherol or N-acetylcysteine did not reveal any protective effects in the P19 neurons. Involvement of mitochondria in the MDMA-induced cytotoxicity was also examined, but MDMA did not alter the mitochondrial membrane potential (ΔΨm) in the P19 neurons. We conclude that MDMA produce a concentration-, time- and temperature-dependent neurotoxicity and our results suggest that the mechanism behind MDMA-induced toxicity in mouse-derived neurons do not involve the serotonergic system, oxidative stress or mitochondrial dysfunction.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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