Modulation of dendritic release of dopamine by metabotropic glutamate receptors in rat substantia nigra |
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Authors: | Campusano Jorge M Abarca Jorge Forray María Inés Gysling Katia Bustos Gonzalo |
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Affiliation: | Laboratory of Biochemical Pharmacology, Department of Cell and Molecular Biology, Faculty of Biological Sciences, Catholic University of Chile, Alameda 340, P.O. Box 114-D, Santiago, Chile. |
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Abstract: | A superfusion system was used to study the effects of metabotropic glutamate receptor (mGluR) ligands upon the release of [(3)H]dopamine ([(3)H]DA) previously taken up by rat substantia nigra (SN) slices. trans-(+/-)-1-Amino-(1S,3R)-cyclopentane dicarboxylic acid (trans-ACPD; 100 and 600 microM), a group I and II mGluR agonist, evoked the release of [(3)H]DA from nigral slices. This last effect was reduced significantly by (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)-glycine (MCCG; 300 microM), an antagonist of group II mGluR, or by the addition of tetrodotoxin (D-APV; 1 microM) to the superfusion medium. D-(-)-2-Amino-5-phosphono-valeric acid (100 microM), an N-methyl-D-aspartate receptor antagonist, or the presence of Mg(2+) (1.2mM) in the superfusion medium did not modify trans-ACPD-induced [(3)H]DA release. In addition, a group II mGluR agonist such as (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-glycine (DCG-IV; 100 microM) significantly induced the release of [(3)H]DA from nigral slices, whereas a group I mGluR agonist such as (RS)-3,5-dihydroxyphenylglycine (DHPG; 50 and 100 microM) did not modify the release of the [(3)H]-amine. Further experiments showed that the NMDA (100 microM)-evoked release of [(3)H]DA was decreased significantly by prior exposure of SN slices to trans-ACPD. Finally, partial denervation of the DA nigro-striatal pathway with 6-hydroxydopamine (6-OH-DA) increased trans-ACPD-induced release of [(3)H]DA, whereas it decreased trans-ACPD inhibitory effects on NMDA-evoked release of [(3)H]DA from nigral slices. The present results suggest that the dendritic release of DA in the SN is regulated by mGluR activation. Such nigral mGluR activation may produce opposite effects upon basal and NMDA-evoked release of DA in the SN. In addition, such mGluR-induced effects in the SN are modified in response to partial denervation of the DA nigro-striatal pathway. |
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Keywords: | SN, substantia nigra DA, dopamine GLU, glutamate iGluR, ionotropic GLU receptor mGluR, metabotropic GLU receptor NMDA, N-methyl- smallcaps" >d-aspartate AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole KRP, Krebs-Ringer-phosphate 6-OH-DA, 6-hydroxydopamine GABA, γ-aminobutyric acid TTX, tetrodotoxin trans-ACPD, trans-(±)-1-amino-(1S,3R)-cyclopentane dicarboxylic acid KA, kainate DHPG, (RS)-3,5-dihydroxyphenylglycine DCG-IV, (2S,1′R,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)-glycine MCCG, (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)-glycine smallcaps" >d-APV, smallcaps" >d-(−)-2-amino-5-phosphono-valeric acid. |
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