Enhanced [3H]DOPA and [3H]dopamine turnover in striatum and frontal cortex in vivo linked to glutamate receptor antagonism

Jakob Reith, Paul Cumming, Albert Gjedde

Research output: Contribution to journalArticle

Abstract

We tested the hypothesis that blockade of NMDA glutamate receptors in brain enhances dopamine turnover. We blocked this class of glutamate receptors in the rat brain in vivo with dizocilpine (MK-801) and measured the accumulation of radiolabeled DOPA and its metabolites as functions of time after intravenous bolus injection. Using the time courses of the accumulated metabolites, we calculated the turnover constants of enzymes mediating dopamine synthesis and catabolism. Dizocilpine treatment for 8 days enhanced the rates of DOPA decarboxylation and dopamine oxidation (mono-amine oxidation) 4-and 16-fold, respectively, in neostriatum and 10- and 3-fold, respectively, in frontal cortex. The findings are not inconsistent with the hypothesis that the psychotomimetic properties of dizocilpine may be the manifestation of denervation hypersensitivity linked to activation of key enzymes of dopamine turnover in striatum.

Original languageEnglish (US)
Pages (from-to)1979-1985
Number of pages7
JournalJournal of Neurochemistry
Volume70
Issue number5
StatePublished - May 1998
Externally publishedYes

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Keywords

  • Dizocilpine
  • DOPA
  • Glutamate receptors
  • N-Methyl-D-aspartate

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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