Ethanol consumption and sedation are altered in mice lacking the glycine receptor α2 subunit.
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
19
11
2019
revised:
31
03
2020
accepted:
09
05
2020
pubmed:
22
5
2020
medline:
22
6
2021
entrez:
22
5
2020
Statut:
ppublish
Résumé
The precise mechanism/s of action of ethanol, although studied for many years, are not well understood. Like other drugs of abuse, ethanol affects dopamine levels in the nucleus accumbens (nAc), an important region of the mesolimbic system, causing a reinforcing effect. It has been shown that glycine receptors (GlyRs) present in the nAc are potentiated by clinically relevant concentrations of ethanol, where α1 and α2 are the predominant subunits expressed. Using a combination of electrophysiology and behavioural assays, we studied the involvement of GlyR α2 subunits on the effects of low and high doses of ethanol, as well as on consumption using mice lacking the GlyR α2 subunit (male Glra2 GlyR α2 subunits exist in accumbal neurons, since the glycine-evoked currents and glycinergic miniature inhibitory postsynaptic currents (mIPSCs) in Glra2 The differences in ethanol consumption between WT and KO mice provide additional evidence supporting the conclusion that GlyRs are biologically relevant targets for the sedative and rewarding properties of ethanol.
Sections du résumé
BACKGROUND AND PURPOSE
The precise mechanism/s of action of ethanol, although studied for many years, are not well understood. Like other drugs of abuse, ethanol affects dopamine levels in the nucleus accumbens (nAc), an important region of the mesolimbic system, causing a reinforcing effect. It has been shown that glycine receptors (GlyRs) present in the nAc are potentiated by clinically relevant concentrations of ethanol, where α1 and α2 are the predominant subunits expressed.
EXPERIMENTAL APPROACH
Using a combination of electrophysiology and behavioural assays, we studied the involvement of GlyR α2 subunits on the effects of low and high doses of ethanol, as well as on consumption using mice lacking the GlyR α2 subunit (male Glra2
KEY RESULTS
GlyR α2 subunits exist in accumbal neurons, since the glycine-evoked currents and glycinergic miniature inhibitory postsynaptic currents (mIPSCs) in Glra2
CONCLUSION AND IMPLICATIONS
The differences in ethanol consumption between WT and KO mice provide additional evidence supporting the conclusion that GlyRs are biologically relevant targets for the sedative and rewarding properties of ethanol.
Identifiants
pubmed: 32436225
doi: 10.1111/bph.15136
pmc: PMC7429487
doi:
Substances chimiques
Glra2 protein, mouse
0
Receptors, Glycine
0
Ethanol
3K9958V90M
Glycine
TE7660XO1C
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3941-3956Subventions
Organisme : NIAAA NIH HHS
ID : R01 AA025718
Pays : United States
Organisme : Medical Research Council
ID : G0500833
Pays : United Kingdom
Informations de copyright
© 2020 The British Pharmacological Society.
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