Abstract

A superfusion system was used to study the effects of metabotropic glutamate receptor (mGluR) ligands upon the release of [3H]dopamine ([3H]DA) previously taken up by rat substantia nigra (SN) slices. trans-(±)-1-Amino-(1S,3R)-cyclopentane dicarboxylic acid (trans-ACPD; 100 and 600?M), a group I and II mGluR agonist, evoked the release of [3H]DA from nigral slices. This last effect was reduced significantly by (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)-glycine (MCCG; 300?M), an antagonist of group II mGluR, or by the addition of tetrodotoxin (D-APV; 1?M) to the superfusion medium. D-(-)-2-Amino-5-phosphono-valeric acid (100?M), an N-methyl-D-aspartate receptor antagonist, or the presence of Mg2+ (1.2mM) in the superfusion medium did not modify trans-ACPD-induced [3H]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?M) significantly induced the release of [3H]DA from nigral slices, whereas a group I mGluR agonist such as (RS)-3,5-dihydroxyphenylglycine (DHPG; 50 and 100?M) did not modify the release of the [3H]-amine. Further experiments showed that the NMDA (100?M)-evoked release of [3H]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 [3H]DA, whereas it decreased trans-ACPD inhibitory effects on NMDA-evoked release of [3H]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. © 2002 Elsevier Science Inc. All rights reserved.