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

24 Scopus citations

Abstract

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
Title of host publicationAnnals of the New York Academy of Sciences
Pages225-233
Number of pages9
Volume1074
DOIs
StatePublished - Aug 1 2006

Publication series

NameAnnals of the New York Academy of Sciences
Volume1074
ISSN (Print)00778923
ISSN (Electronic)17496632

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Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Anderson, K. L., & Itzhak, Y. (2006). Methamphetamine-induced selective dopaminergic neurotoxicity is accompanied by an increase in striatal nitrate in the mouse. In Annals of the New York Academy of Sciences (Vol. 1074, pp. 225-233). (Annals of the New York Academy of Sciences; Vol. 1074). https://doi.org/10.1196/annals.1369.021