Contribution of GlyR α3 Subunits to the Sensitivity and Effect of Ethanol in the Nucleus Accumbens

Loreto S San Martin; Lorena Armijo-Weingart; Anibal Araya; Gonzalo E Yévenes; Robert J Harvey; Luis G Aguayo

doi:10.3389/fnmol.2021.756607

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Contribution of GlyR α3 Subunits to the Sensitivity and Effect of Ethanol in the Nucleus Accumbens

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Contribution of GlyR α3 Subunits to the Sensitivity and Effect of Ethanol in the Nucleus Accumbens

Loreto S San Martin, Lorena Armijo-Weingart, Anibal Araya, Gonzalo E Yévenes, Robert J Harvey and Luis G Aguayo

Frontiers in Molecular Neuroscience, Vol.14, pp.1-22

2021

DOI: https://doi.org/10.3389/fnmol.2021.756607

PMCID: PMC8570041

PMID: 34744627

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Abstract

Laboratories

Ethanol

Neurons

Spinal cord

Drinking behaviour

Nucleus accumbens

Neurotransmission

Picrotoxin

Glucose

Addictive Behaviors

Brain stem; - Aminobutyric acid A receptors; Righting reflex; Reinforcement

The glycine receptor (GlyR), a ligand-gated ion channel, is critical for inhibitory neurotransmission in brainstem, spinal cord, and in supraspinal regions. Recent data from several laboratories have shown that GlyRs are expressed in the brain reward circuitry and that α1 and α2 are the principal subunits expressed in the nucleus accumbens (nAc). In the present study, we studied the sensitivity to ethanol of homomeric and heteromeric α3 GlyR subunits in HEK293 cells and dissociated neurons from the nAc. Finally, we explored ethanol-related behaviors in a Glra3 knockout mouse (Glra3–/–). Studies in HEK293 cells showed that while homomeric α3 GlyR subunits were insensitive to ethanol, heteromeric α3β GlyR subunits showed higher sensitivity to ethanol. Additionally, using electrophysiological recordings in dissociated accumbal neurons, we found that the glycine current density increased in Glra3–/– mice and the GlyRs were less affected by ethanol and picrotoxin. We also examined the effect of ethanol on sedation and drinking behavior in Glra3–/– mice and found that the duration in the loss of righting reflex (LORR) was unchanged compared to wild-type (WT) mice. On the other hand, using the drinking in the dark (DID) paradigm, we found that Glra3–/– mice have a larger ethanol consumption compared to WT mice, and that this was already high during the first days of exposure to ethanol. Our results support the conclusion that heteromeric α3β, but not homomeric α3, GlyRs are potentiated by ethanol. Also, the increase in GlyR and GABAAR mediated current densities in accumbal neurons in the KO mice support the presence of compensatory changes to α3 knock out. The increase in ethanol drinking in the Glra3–/– mice might be associated to the reduction in β and compensatory changes in other subunits in the receptor arrangement.

Details

Title: Contribution of GlyR α3 Subunits to the Sensitivity and Effect of Ethanol in the Nucleus Accumbens
Authors: Loreto S San Martin (Author) - Universidad de Concepción del Uruguay
Lorena Armijo-Weingart (Author) - Universidad de Concepción del Uruguay
Anibal Araya (Author) - Universidad de Concepción del Uruguay
Gonzalo E Yévenes (Author) - Universidad de Concepción del Uruguay
Robert J Harvey (Author) - University of the Sunshine Coast, Queensland, School of Health and Behavioural Sciences - Legacy
Luis G Aguayo (Corresponding Author) - Universidad de Concepción del Uruguay
Publication details: Frontiers in Molecular Neuroscience, Vol.14, pp.1-22
Publisher: Frontiers Research Foundation
Date published: 2021
DOI: 10.3389/fnmol.2021.756607
ISSN: 1662-5099
PMID: 34744627; PMC8570041
Copyright note: Copyright © 2021 San Martin, Armijo-Weingart, Araya, Yévenes, Harvey and Aguayo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99586007202621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Neurosciences

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