title: Role of excitatory amino acids in the direct and indirect presynaptic regulation of dopamine release from nerve terminals of nigrostriatal dopaminergic neurons.
abstract: In vivo experiments carried out in halothane-anaesthetized cats implanted with push-pull cannulae demonstrated that glutamate (GLU) released from corticostriatal fibers triggers the release of dopamine (DA), even in the absence of activity in nigral DA cells. As shown in vitro, using rat striatal slices or synaptosomes or in vivo in the cat, both NMDA and AMPA receptors subtypes are involved in the GLU-induced release of DA. Beside this direct regulation, GLU also exert several indirect facilitatory and inhibitory controls on DA release, particularly through cholinergic and GABAergic striatal neurons. Indeed, as shown by numerous authors, the GLU-evoked release of DA is markedly reduced in the presence of tetrodotoxin, bicuculline or atropine or by previous kainate- or ibotenate-induced lesion of striatum. Differences in the presynaptic regulation of DA release in striosomal and matrix compartments have also been found with NMDA and acetylcholine. The effect of acetylcholine was of shorter duration in the matrix than in the striosomal-enriched areas. Two opposite indirect regulations of DA release could be demonstrated: one is facilitatory and involves nicotinic receptors, the other is inhibitory, involves muscarinic receptors and mediated, at least in the matrix by dynorphin containing neurons. The NMDA-evoked responses are of larger amplitude and more sensitive to tetrodotoxin in the matrix than in the striosomes. In conclusion, GLU released from corticostriatal fibers, is able to control the release of DA from terminals of nigrostriatal neurons through direct facilitatory mechanisms (NMDA and AMPA receptors), but also through indirect facilitatory and inhibitory local circuits involving cholinergic and GABAergic neurons.
authors.affiliation: Chaire de Neuropharmacologie, Collège de France, INSERM U114, 11 Place Marcelin-Berthelot, F-75231, Paris Cedex 05, France.
authors.forename: A
authors.initials: A
authors.lastname: Cheramy
authors.forename: M L
authors.initials: ML
authors.lastname: Kemel
authors.forename: C
authors.initials: C
authors.lastname: Gauchy
authors.forename: J M
authors.initials: JM
authors.lastname: Desce
authors.forename: T
authors.initials: T
authors.lastname: Galli
authors.forename: L
authors.initials: L
authors.lastname: Barbeito
authors.forename: J
authors.initials: J
authors.lastname: Glowinski