The abused drug MDMA (Ecstasy) induces programmed death of human serotonergic cells.
The widely abused amphetamine analog 3,4-methylenedioxymethamphetamine (MDMA, also called "ecstasy") induces hallucination and psychostimulation, as well as long-term neuropsychiatric behaviors such as panic and psychosis. In rodents and monkeys, MDMA is cytotoxic to serotonergic neurons, but this is less clear with humans. Herein, MDMA was cytotoxic to human serotonergic JAR cells; it altered the cell cycle, increased G2/M phase arrest, and induced DNA fragmentation in a cycloheximide-sensitive way. This apoptosis was not observed in nonserotonergic human NMB cells. The stereospecific effect of amphetamines in JAR cells, and the key role of NO and dopamine in MDMA-induced apoptosis were determined. The relevancy of MDMA-induced cell death to drug users is discussed.
Simantov
R
R
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Tauber
M
M
D017209:Apoptosis / Q000187:drug effects*; D002395:Catecholamines / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002822:Choriocarcinoma; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D006801:Humans; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009569:Nitric Oxide / Q000502:physiology; D018490:Serotonin Agents / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms
D002395:Catecholamines; D018490:Serotonin Agents; D009569:Nitric Oxide; D018817:N-Methyl-3,4-methylenedioxyamphetamine