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

Content Provider	Europe PMC
Author	Spencer, FelicityS. E. Glodkowska, Maria Sebold, Anna I. Yavas, Ersin Young, Andrew M. J.
Copyright Year	2023
Abstract	Electrically stimulated dopamine release from the nucleusaccumbensis attenuated following application of N-methyl-d-aspartate (NMDA), which is likely to be mediated indirectlythrough intermediary neuronal mechanisms rather than by a direct actionon dopamine terminals. On the basis of known modulatory processesin nucleus accumbens, the current experiments sought to test whetherthe effect of NMDA was mediated through cholinergic, GABA-ergic, ormetabotropic glutamatergic intermediate mechanisms. Fast-scan cyclicvoltammetry was used to measure electrically stimulated dopamine releasein nucleus accumbens of rat brain slices in vitro. Stimulated dopamine release was attenuated by NMDA, confirming previousfindings, but this attenuation was unaffected by either cholinergicor GABA-ergic antagonists. However, it was completely abolished bythe nonselective group I/II/III metabotropic glutamate receptor antagonistα-methyl-4-carboxyphenylglycine (MCPG) and by the selectivegroup II antagonist LY 341396. Therefore, group II metabotropic glutamatereceptors, but not acetylcholine or GABA receptors, mediate the attenuationof stimulated dopamine release caused by NMDA, probably by presynapticinhibition through receptors located extra-synaptically on dopamineterminals. This provides a plausible mechanism for the documentedrole of metabotropic glutamate receptor systems in restoring deficitsinduced by NMDA receptor antagonists, modeling schizophrenia, underliningthe potential for drugs affecting these receptors as therapeutic agentsin treating schizophrenia.
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Journal	ACS Chemical Neuroscience [ACS Chem Neurosci]
DOI	10.1021/acschemneuro.2c00777
PubMed Central reference number	PMC10119936
Issue Number	8
PubMed reference number	37022746
e-ISSN	19487193
Language	English
Publisher	American Chemical Society
Publisher Date	2023-04-06
Access Restriction	Open
Rights License	Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). © 2023 The Authors. Published by American Chemical Society
Subject Keyword	Brain slices dopamine fast-scan cyclic voltammetry metabotropic glutamate receptors N-methyl-d-aspartate (NMDA) nucleus accumbens
Content Type	Text
Resource Type	Article
Subject	Biochemistry Cell Biology Physiology Medicine Cognitive Neuroscience