AMPA receptor blockade potentiates the stimulatory effect of L-DOPA on dopamine release in dopamine-deficient corticostriatal slice preparation

Crit Rev Neurobiol. 2004;16(1-2):129-39. doi: 10.1615/critrevneurobiol.v16.i12.140.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Benzodiazepines / pharmacology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Dopamine / deficiency*
  • Dopamine / metabolism*
  • Dopamine Agents / pharmacology*
  • Electric Stimulation
  • Homovanillic Acid / metabolism
  • In Vitro Techniques
  • Levodopa / pharmacology*
  • Neostriatum / drug effects
  • Neostriatum / metabolism*
  • Oxidopamine / toxicity
  • Rats
  • Receptors, AMPA / antagonists & inhibitors*
  • Sympatholytics / toxicity


  • Dopamine Agents
  • Receptors, AMPA
  • Sympatholytics
  • 3,4-Dihydroxyphenylacetic Acid
  • Benzodiazepines
  • Levodopa
  • Oxidopamine
  • talampanel
  • Dopamine
  • Homovanillic Acid