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spencer-et-al-2023-attenuation-of-stimulated-accumbal-dopamine-release-by-nmda-is-mediated-through-metabotropic.pdf (5.35 MB)

Attenuation of Stimulated Accumbal Dopamine Release by NMDA Is Mediated through Metabotropic Glutamate Receptors

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posted on 2023-12-08, 16:22 authored by FSE Spencer, M Glodkowska, AI Sebold, E Yavas, AMJ Young

Electrically stimulated dopamine release from the nucleus accumbens is attenuated following application of N-methyl-d-aspartate (NMDA), which is likely to be mediated indirectly through intermediary neuronal mechanisms rather than by a direct action on dopamine terminals. On the basis of known modulatory processes in nucleus accumbens, the current experiments sought to test whether the effect of NMDA was mediated through cholinergic, GABA-ergic, or metabotropic glutamatergic intermediate mechanisms. Fast-scan cyclic voltammetry was used to measure electrically stimulated dopamine release in nucleus accumbens of rat brain slices in vitro. Stimulated dopamine release was attenuated by NMDA, confirming previous findings, but this attenuation was unaffected by either cholinergic or GABA-ergic antagonists. However, it was completely abolished by the nonselective group I/II/III metabotropic glutamate receptor antagonist α-methyl-4-carboxyphenylglycine (MCPG) and by the selective group II antagonist LY 341396. Therefore, group II metabotropic glutamate receptors, but not acetylcholine or GABA receptors, mediate the attenuation of stimulated dopamine release caused by NMDA, probably by presynaptic inhibition through receptors located extra-synaptically on dopamine terminals. This provides a plausible mechanism for the documented role of metabotropic glutamate receptor systems in restoring deficits induced by NMDA receptor antagonists, modeling schizophrenia, underlining the potential for drugs affecting these receptors as therapeutic agents in treating schizophrenia.

History

Author affiliation

School of Psychology and Vision Science, University of Leicester

Version

  • VoR (Version of Record)

Published in

ACS Chemical Neuroscience

Volume

14

Issue

8

Pagination

1449 - 1458

Publisher

American Chemical Society (ACS)

issn

1948-7193

eissn

1948-7193

Copyright date

2023

Available date

2023-12-08

Spatial coverage

United States

Language

eng

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