Superoxide radicals are mediators of the effects of methamphetamine on Zif268 (Egr-1, NGFI-A) in the brain: Evidence from using CuZn superoxide dismutase transgenic mice

Hiroshi Hirata, Masato Asanuma, Jean Lud Cadet

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Administration of methamphetamine (METH) to mammals is known to cause deleterious effects to brain monoaminergic systems. These toxic effects are thought to be due to oxidative stress. Acute administration of METH causes activation of immediate-early genes (IEGs) such as c-fos and Zif268 mRNA in rodent brains. However, the exact mechanisms involved in these changes have not been completely clarified. As a first step towards assessing a possible role for free radicals in METH-induced changes in IEGs, we have used CuZn superoxide dismutase (SOD) transgenic (Tg) mice and have quantified the effects of METH on c-fos and Zif268 mRNAs by in situ hybridization techniques. Mice were injected with 25 mg/kg of METH and sacrificed at various time points afterwards. There were significant METH-induced increases in both c-fos and Zif268 mRNAs in the frontal cortex and striatum of both strains of animals. Interestingly, the increases in Zif268 were markedly attenuated in the CuZn SOD-Tg mice; the increases in c-fos were also attenuated, but to a significantly lesser degree. These results indicate that superoxide radicals might play an important role in the activation of Zif268 after METH administration. Because IEGs are modulators of gene expression, these results also raise the possibility that oxidative mechanisms might be important factors in neuroadaptive changes caused by stimulant drugs.

Original languageEnglish
Pages (from-to)209-216
Number of pages8
JournalMolecular Brain Research
Volume58
Issue number1-2
DOIs
Publication statusPublished - Jul 15 1998
Externally publishedYes

Keywords

  • Egr-1
  • Methamphetamine
  • Oxidative stress
  • Zif268 mRNA
  • c-fos mRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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