A rapid oxidation and persistent decrease in the vesicular monoamine transporter 2 after methamphetamine

David J. Eyerman, Bryan K. Yamamoto

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Methamphetamine (METH) produces long-term decreases in markers of dopamine (DA) terminals in animals and humans. A decrease in the function of the vesicular monoamine transporter 2 (VMAT2) has been associated with damage to striatal DA terminals caused by METH; however, a possible mechanism for this decrease in VMAT2 function has not been defined. The current study showed that METH caused a rapid decrease to 68% of controls in VMAT2 protein immunoreactivity of the vesicular fraction from striatal synaptosomes within 1 h after a repeated high-dose administration regimen of METH. This decrease was associated with a 75% increase in nitrosylation of VMAT2 protein in the synaptosomal fraction as measured by nitrosocysteine immunoreactivity of VMAT2 protein. The rapid decreases in VMAT2 persisted when evaluated 7 days later and were illustrated by decreases in VMAT2 immunoreactivity and DA content of the vesicular fraction to 34% and 51% of control values, respectively. The decreases were blocked or attenuated by prior injections of the neuronal nitric oxide synthase inhibitor, S-methyl-l-thiocitrulline. These studies demonstrate that METH causes a rapid neuronal nitric oxide synthase-dependent oxidation of VMAT2 and long-term decreases in VMAT2 protein and function. The results also suggest that surviving DA terminals after METH exposure may have a compromised capacity to buffer cytosolic DA concentrations and DA-derived oxidative stress.

Original languageEnglish (US)
Pages (from-to)1219-1227
Number of pages9
JournalJournal of Neurochemistry
Volume103
Issue number3
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

Keywords

  • Dopamine
  • Methamphetamine
  • Nitric oxide
  • Vesicle
  • Vesicular monoamine transporter 2

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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