Modulation of Dendritic Release of Dopamine by N‐Methyl‐D‐Aspartate Receptors in Rat Substantia Nigra

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Abstract
A superfusion system was used to study the effects of excitatory amino acids (EAA) on release of [3H]dopamine ([3H]DA) previously taken up by rat substantia nigra (SN) slices. The EAA tested (20–250 μM), with the exception of quisqualate and kainate, markedly evoked [3H]DA release from nigral slices when Mg2+ ions were omitted from the superfusion medium. The EAA receptor agonists exhibited the following relative potency in stimulating [3H]DA release: l-glutamate (L-Glu) > N-methyl-d-aspartate (NMDA) > NM(D,L)A > d-Glu ≫ quisqualate = kainate. d-2-Amino-5-phosphonovalerate (100–200 μ.M), an antagonist for NMDA receptors, substantially reduced [3H]DA release evoked by l-Glu or NMDA. In contrast, l-Glu diethyl ester (100–200 μM) produced a lesser blocking effect on [3H]DA release evoked by the EAA. Further experiments showed that the NMDA-mediated release of [3H]DA was totally suppressed by the omission of Ca2+ or by the addition of tetrodotoxin (0.1 μM) to the superfusion medium. In addition, strychnine, an antagonist for glycine (Gly) receptors, significantly decreased NMDA (100 μM)-evoked as well as glycine (100 μM-evoked release of [3H]DA from nigral slices. The results shown support the idea that activation of NMDA subtype receptors in SN may trigger a Ca2+-dependent release of DA from dendrites of nigro-striatal DA-containing neurons. Furthermore, a transsynaptic mechanism that may partially involve Gly-containing interneurons is proposed to account for some of the events mediating NMDA receptor activation and DA release in SN.