AMPA receptor blockade potentiates the stimulatory effect of L-DOPA on dopamine release in dopamine-deficient corticostriatal slice preparation.
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.
Juranyi
Zsolt
Z
Division of Preclinical Research, EGIS Pharmaceuticals Ltd., Budapest, Hungary. lharsing@axelero.hu
Sziray
Nora
N
Marko
Bernadett
B
Levay
Gyorgy
G
Harsing
Laszlo G
LG
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000172:deficiency* / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D006719:Homovanillic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007980:Levodopa / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D013565:Sympatholytics / Q000633:toxicity
D015259:Dopamine Agents; D018091:Receptors, AMPA; D013565:Sympatholytics; D015102:3,4-Dihydroxyphenylacetic Acid; D001569:Benzodiazepines; D007980:Levodopa; D016627:Oxidopamine; C085266:talampanel; D004298:Dopamine; D006719:Homovanillic Acid