Amphetamines induce apoptosis and regulation of bcl‐x splice variants in neocortical neurons

作者：Gabriele Stumm, Jürgen Schlegel, Theo Schäfer, C. Würz, Hans Dieter Mennel, Jürgen C. Krieg, Helmut Vedder · 发表于：The FASEB Journal · 年份：1999 · DOI：10.1096/fasebj.13.9.1065 · 被引用次数：177 · 研究领域：Forensic Toxicology and Drug Analysis、Neurotransmitter Receptor Influence on Behavior、Cannabis and Cannabinoid Research

Amphetamineanalogs have emerged as popular recreational drugs of abuse. The number of reports of these substances producing severe acute toxicity and death is increasing. In 'Ecstasy' -associated deaths, focal necrosis in the liver and individual myocytic necrosis has been reported. Furthermore, serotonergic and dopaminergic neuronal cell damage has been observed in experimental amphetamine intoxication in laboratory animals. Here we demonstrate that subchronic exposure to D-amphetamine, methamphetamine, methylenedioxyamphetamine, and methylenedioxymethamphetamine ('Ecstasy') results in significant neurotoxicity in rat neocortical neurons in vitro. This neuronal cell death is accompanied by endonucleosomal DNA cleavage and differential expression of anti- and proapoptotic bcl-xL/S splice variants. In addition, we observed pronounced induction of cell stress-associated transcription factor c-jun and translation initiation inhibitor p97 after amphetamine treatment. These data support that the neurotoxic effects of different amphetamines are extended to rat neocortical neurons and that apoptotic pathways are involved in amphetamine-induced neurotoxicity.