Involvement of oxidative and L-arginine-NO pathways in the neurotoxicity of drugs of abuse in vitro.
1. Inhibitors of nitric oxide (NO) formation or ADP-ribosylation attenuate methamphetamine (METH)- and methylenedioxymetamphetamine (MDMA)-induced neurotoxicity on dopaminergic and serotonergic cells in primary cultures. 2. They also prevent METH-induced reactive gliosis in dopaminergic cultures. 3. Overexpression of superoxide dismutase (SOD) in cells obtained from SOD-transgenic mice also attenuates drug-induced toxicity. 4. These data indicate a role for oxygen-based and NO free radicals in the mechanisms of cell death associated with drugs of abuse in vitro.
Cerruti
C
C
Molecular Neuropsychiatry Section, NIH/NIDA/Division of Intramural Research, Baltimore, Maryland 21224, USA.
Sheng
P
P
Ladenheim
B
B
Epstein
C J
CJ
Cadet
J L
JL
D000246:Adenosine Diphosphate Ribose / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000633:toxicity; D005260:Female; D005609:Free Radicals; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005911:Gliosis / Q000517:prevention & control; D013287:Illicit Drugs / Q000633:toxicity*; D008694:Methamphetamine / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D011247:Pregnancy; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000633:toxicity; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D015259:Dopamine Agents; D005609:Free Radicals; D013287:Illicit Drugs; D018490:Serotonin Agents; D000246:Adenosine Diphosphate Ribose; D009569:Nitric Oxide; D012701:Serotonin; D008694:Methamphetamine; D001120:Arginine; D013482:Superoxide Dismutase; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine