In Vitro Release of Endogenous Dopamine from the Striatum of the Weaver Mutant Mouse

J. R. Simon, H. Yu, J. A. Richter, M. R. Vasko, B. Ghetti

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The weaver mutant mouse has a genetically determined defect in the nigrostriatal dopaminergic system. The present study was undertaken to test the hypothesis that in the weaver mutant mouse, striatal nerve terminals undergo compensatory changes in response to this deficiency. To test this hypothesis, we studied the basal and stimulated release of dopamine from striatal slices of weaver mutant mice and matched controls. By using a superfusion system and concentrating the superfusate by passage over alumina, resting dopamine release could be determined in the weaver mutant despite the fact that striatal tissue content of dopamine in these mice is reduced by >75% compared with control mice. Fractional resting release of dopamine in weaver striatal slices was significantly elevated compared with that in controls, suggesting that the release mechanisms in the weaver may be adapting to overcome the dopamine deficit. Potassium-evoked release (24 and 48 mM potassium) was not significantly different between the two genotypes. In contrast, amphetamine-evoked release (1 μM) was significantly greater in the weaver mice than in controls. In both genotypes, release evoked by amphetamine was completely inhibited by cocaine, implicating the dopamine uptake carrier in this release process. These findings suggest that fundamental differences in dopamine release mechanisms exist between weaver and control mice and support the hypothesis that compensatory mechanisms may develop in neurons in response to dopamine deficits.

Original languageEnglish (US)
Pages (from-to)1478-1482
Number of pages5
JournalJournal of Neurochemistry
Volume57
Issue number5
DOIs
StatePublished - Nov 1991

Keywords

  • Dopamine
  • Dopamine release
  • Release
  • Striatum
  • Weaver

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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