Dynamic changes in vesicular glutamate transporter 1 function and expression related to methamphetamine-induced glutamate release

Karla A. Mark, Maria S. Quinton, Shelley J. Russek, Bryan K. Yamamoto

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

The vesicular glutamate (GLU) transporter (VGLUT1) is a critical component of glutamatergic neurons that regulates GLU release. Despite the likely role of GLU release in drug abuse pathology, there is no information that links VGLUT1 with drugs of abuse. This study provides the first evidence that methamphetamine (METH) alters the dynamic regulation of striatal VGLUT1 function and expression through a polysynaptic pathway. METH increases cortical VGLUT1 mRNA, striatal VGLUT1 protein in subcellular fractions, and theVmax of striatal vesicular GLU uptake. METH also increases glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein in the crude vesicle fraction. METH-induced increases in cortical VGLUT1 mRNA, as well as striatal VGLUT1 and GAPDH, are GABAA receptor-dependent because they are blocked by GABAA receptor antagonism in the substantia nigra. These results show that VGLUT1 can be dynamically regulated via a polysynaptic pathway to facilitate vesicular accumulation of GLU for subsequent release after METH.

Original languageEnglish (US)
Pages (from-to)6823-6831
Number of pages9
JournalJournal of Neuroscience
Volume27
Issue number25
DOIs
StatePublished - Jun 20 2007

Keywords

  • Basal ganglia
  • Glutamate
  • Methamphetamine
  • Striatum
  • Substantia nigra
  • VGLUT1

ASJC Scopus subject areas

  • Neuroscience(all)

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