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Presence of ethanol-sensitive and ethanol-insensitive glycine receptors in the ventral tegmental area and prefrontal cortex in mice2.97 MB
Published VersionCC BY V4.0, Open Access
Journal article
Presence of ethanol-sensitive and ethanol-insensitive glycine receptors in the ventral tegmental area and prefrontal cortex in mice
British Journal of Pharmacology, Vol.178(23), pp.4691-4707
2021
Abstract
Background and Purpose:
Glycine receptors composed of α1 and β subunits are primarily found in the spinal cord and brainstem and are potentiated by ethanol (10–100 mM). However, much less is known about the presence, composition and ethanol sensitivity of these receptors in higher CNS regions. Here, we examined two regions of the brain reward system, the ventral tegmental area (VTA) and the prefrontal cortex (PFC), to determine their glycine receptor subunit composition and sensitivity to ethanol.
Experimental Approach:
We used Western blot, immunohistochemistry and electrophysiological techniques in three different models: wild-type C57BL/6, glycine receptor subunit α1 knock-in and glycine receptor subunit α2 knockout mice.
Key Results:
Similar levels of α and β receptor subunits were detected in both brain regions, and electrophysiological recordings demonstrated the presence of glycine-activated currents in both areas. Sensitivity of glycine receptors to glycine was lower in the PFC compared with VTA. Picrotoxin only partly blocked the glycine-activated current in the PFC and VTA, indicating that both regions express heteromeric αβ receptors. Glycine receptors in VTA neurons, but not in PFC neurons, were potentiated by ethanol.
Conclusion and Implications:
Glycine receptors in VTA neurons from WT and α2 KO mice were potentiated by ethanol, but not in neurons from the α1 KI mice, supporting the conclusion that α1 glycine receptors are predominantly expressed in the VTA. By contrast, glycine receptors in PFC neurons were not potentiated in any of the mouse models studied, suggesting the presence of α2/α3/α4, rather than α1 glycine receptor subunits.
Details
- Title
- Presence of ethanol-sensitive and ethanol-insensitive glycine receptors in the ventral tegmental area and prefrontal cortex in mice
- Authors
- Anibal Araya (Author) - Universidad de Concepción del UruguayScarlet Gallegos (Author) - Universidad de Concepción del UruguayRodrigo Viveros (Author) - Universidad de Concepción del UruguayLoreto San Martin (Author) - Universidad de Concepción del UruguayBraulio Muñoz (Author) - Universidad de Concepción del UruguayRobert Harvey (Author) - University of the Sunshine Coast, Queensland, School of Health and Behavioural Sciences - LegacyHans U Zeilhofer (Author) - University of ZurichLuis G Aguayo (Corresponding Author) - Universidad de Concepción del Uruguay
- Publication details
- British Journal of Pharmacology, Vol.178(23), pp.4691-4707
- Publisher
- John Wiley & Sons Ltd.
- Date published
- 2021
- DOI
- 10.1111/bph.15649
- ISSN
- 1476-5381; 0007-1188
- Copyright note
- © 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- 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
- 99570208102621
- Output Type
- Journal article
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