Methamphetamine-induced increase in striatal NF-kappaB DNA-binding activity is attenuated in superoxide dismutase transgenic mice.
Methamphetamine injection (x4 with 2-h interval) caused dose-dependent activation of striatal NF-kappaB activity. Striatal NF-kappaB binding increased significantly at 1-3 h after the last injection of methamphetamine (10 mg/kg, i.p. x4). This induction of striatal NF-kappaB activity was significantly attenuated in Cu, Zn-superoxide dismutase transgenic mice in a gene dosage-dependent fashion. The present results suggest that reactive oxygen species generated by methamphetamine injections can activate striatal NF-kappaB DNA-binding during this drug-induced toxic process.
Molecular Neuropsychiatry Section, NIH/ NIDA, Intramural Research Program, P.O. Box 5180, Baltimore, MD, USA.
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Asanuma
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Cadet
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018628:Gene Dosage; D005786:Gene Expression Regulation / Q000187:drug effects; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D008694:Methamphetamine; D013482:Superoxide Dismutase