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ISSN: 0892-0915 Print
DOI: 10.1615/CritRevNeurobiol.v16.i12
Pages: 194
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DOI: 10.1615/CritRevNeurobiol.v16.i12.140
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Article price - $35.00 |
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AMPA Receptor Blockade Potentiates the Stimulatory Effect of L-DOPA on Dopamine Release in Dopamine-Deficient Corticostriatal Slice Preparation
Zsolt Juranyi
Division of Preclinical Research, EGIS Pharmaceuticals Ltd., Budapest, Hungary
Nora Sziray
Division of Preclinical Research, EGIS Pharmaceuticals Ltd., Budapest, Hungary
Bernadett Marko
Division of Preclinical Research, EGIS Pharmaceuticals Ltd., Budapest, Hungary
Gyorgy Levay
Division of Preclinical Research, EGIS Pharmaceuticals Ltd., Budapest, Hungary
Laszlo G. Harsing,Jr.
Division of Preclinical Research, EGIS Pharmaceuticals Ltd., Budapest, Hungary
ABSTRACT
The release of [3H]dopamine was measured in rat corticostriatal slice preparations that contained the striatum and the adjacent prefrontal cortex to maintained glutamatergic corticostriatal afferentation. These slices were prepared from either nontreated or 6-hydroxydopamine—pretreated rats. The slices were loaded with [3H]dopamine, submerged in a two-compartment bath so that the cortical region was contained in one compartment, the corpus callosum was passed through a silicone greased slot, and the striatal region was contained in the other compartment. The cortical and the striatal parts were superfused with Krebs-bicarbonate buffer independently. The release of [3H]dopamine was determined from the striatal part at rest and in response to electrical stimulation of the cortical area. Electrical stimulation of the cortical part increased the release of [3H]dopamine from the striatal part of the slices, and this release was found to be higher after lesion of the nigrostriatal dopaminergic pathway with 6-hydroxydopamine. Cortically evoked [3H]dopamine release was even higher in the presence of the dopamine precursor L-DOPA after 6-hydroxdopamine lesion. Perfusion of GYKI-53405, a noncompetitive AMPA receptor antagonist, in combination with L-DOPA further increased both basal and stimulation-evoked [3H]dopamine release, whereas GYKI-53405 by itself did not influence basal [3H]dopamine outflow from striatum. These findings indicate that, in parkinsonian striatum, the stimulatory effect of L-DOPA on dopamine release is potentiated by AMPA receptor blockade, and the antiparkinsonian effect of GYKI-53405 may be due to its L-DOPA sparing effect.
pages 129-139
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