The abused drug MDMA (Ecstasy) induces programmed death of human serotonergic cells

MDMA (ecstasy), an amphetamine analog that causes hallucination and psychostimulation, can trigger programmed cell death (apoptosis) in human serotonergic JAR cells. The drug altered the cell cycle, increased G2/M phase arrest, and caused DNA fragmentation, effects that were blocked by cycloheximide. This apoptosis did not occur in nonserotonergic human NMB cells. The process depended on nitric oxide and dopamine and was stereospecific for amphetamines. The findings suggest a mechanism for long-term neuropsychiatric effects in users, though direct evidence in human neurons remains unclear.

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Abstract

The widely abused amphetamine analog 3,4‐methylenecdioxymethamphetamine (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., Tauber, M. The abused drug MDMA (Ecstasy) induces programmed death of human serotonergic cells. FASEB J. 11, 141‐146(1997)