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Amphetamines induce apoptosis and regulation of bcl‐x splice variants in neocortical neurons
Author(s) -
Stumm G.,
Schlegel J.,
Schäfer T.,
Würz C.,
Mennel H. D.,
Krieg J.C.,
Vedder H.
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.9.1065
Subject(s) - neurotoxicity , methamphetamine , amphetamine , programmed cell death , dopaminergic , apoptosis , meth , pharmacology , serotonergic , biology , ecstasy , toxicity , mdma , neuroscience , microbiology and biotechnology , chemistry , medicine , dopamine , biochemistry , serotonin , psychiatry , monomer , organic chemistry , acrylate , polymer , receptor
Amphetamine analogs 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‐x L/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.—Stumm, G., Schlegel, J., Schäfer, T., Würz, C., Mennel, H. D., Krieg, J.‐C., Vedder, H. Amphetamines induce apoptosis and regulation of bcl‐x splice variants in neocortical neurons. FASEB J. 13, 1065–1072 (1999)