Methamphetamine-induced selective dopaminergic neurotoxicity is accompanied by an increase in striatal nitrate in the mouse

Karen L. Anderson, Yossef Itzhak

Research output: Chapter in Book/Report/Conference proceedingConference contribution

25 Scopus citations


Exposure to high doses of methamphetamine (METH), a major drug of abuse, may cause neuronal damage. Previous studies have implicated the role of peroxynitrite, produced by nitric oxide (NO) and reactive oxygen species, in dopaminergic neurotoxicity produced by METH in mice. The present article was undertaken to investigate if a neurotoxic regimen of METH is associated with changes in tissue levels of nitrate and nitrite, which are the stable products of NO. Administration of METH (5 mg/kg × 3) to Swiss Webster mice resulted in marked depletion of dopamine (DA) and DA transporter (DAT) binding sites but no change in 5-hydroxytryptamine (5-HT) and 5-HT transporter (5-HTT) binding sites in the striatum, amygdala, frontal cortex, and hippocampus, suggesting that METH causes selective neurotoxicity to DA nerve terminals. The concentration of nitrate in the striatum was increased by about two-fold after METH administration; however, no changes in nitrate concentration were detected in other brain regions that endured dopaminergic neurotoxicity. These findings suggest that (a) a neurotoxic regimen of METH produces selective increase in NO in the striatum, which may generate toxic species such as peroxynitrite, and (b) toxins other than NO-related derivatives may mediate dopaminergic neurotoxicity in the amygdala and frontal cortex.

Original languageEnglish (US)
Title of host publicationCellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity
Subtitle of host publicationCocaine, GHB, and Substituted Amphetamines
PublisherBlackwell Publishing Inc.
Number of pages9
ISBN (Print)1573316296, 9781573316293
StatePublished - Aug 2006

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • Dopamine
  • Methamphetamine
  • Neurotoxicity
  • Nitrate
  • Nitric oxide (NO)
  • Nitrite
  • Peroxynitrite
  • Serotonin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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