Journal article
Ethanol consumption and sedation are altered in mice lacking the glycine receptor α2 subunit
British Journal of Pharmacology, Vol.177(17), pp.3941-3956
2020
PMCID: PMC7429487
PMID: 32436225
Abstract
The sites and actions of ethanol in the central nervous system have been studied for many years, yet the precise mechanisms for its actions are not well understood. For example, like other drugs of abuse, it affects dopamine levels in the nucleus accumbens (nAc), an important region of the mesolimbic system, causing a reinforcing effect. Previous studies have 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 behavioral assays, we studied the involvement of GlyR α2 subunits on the effects of low and high doses of ethanol, as well as in consumption using mice lacking GlyR α2 subunits (male Glra2 and female Glra2 ). Our results support the existence of GlyR α2 subunits in accumbal neurons, since the glycine-evoked currents and glycinergic mIPSCs in the Glra2 mice were drastically decreased. Regarding ethanol effects, we found differences in behavioral studies for ethanol consumption and sedation between WT and Glra2 knockout mice. For example, using the drinking in the dark (DID) paradigm, we found that Glra2 mice presented a binge-like drinking behavior immediately when exposed to ethanol and not a gradual consumption like wild-type animals. Interestingly, the effect of knocking out the Glra2 gene in female (Glra2 ) mice was less evident, since wild-type female mice already showed higher DID. The differences in ethanol consumption between WT and KO mice provide additional evidence supporting the conclusion that GlyRs are biologically-relevant targets for sedative and rewarding properties of ethanol.
Details
- Title
- Ethanol consumption and sedation are altered in mice lacking the glycine receptor α2 subunit
- Authors
- Loreto San Martin (Author) - Universidad de Concepción del UruguayScarlet Gallegos (Author) - Universidad de Concepción del UruguayAnibal Araya (Author) - Universidad de Concepción del UruguayNicol Romero (Author) - Universidad de Concepción del UruguayGiovanni Morelli (Author) - BIOMEDJoris Comhair (Author) - BIOMEDRobert J Harvey (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - LegacyJean-Michel Rigo (Author) - BIOMEDBrône Bert (Author) - BIOMEDLuis G Aguayo (Corresponding Author) - Universidad de Concepción del Uruguay
- Publication details
- British Journal of Pharmacology, Vol.177(17), pp.3941-3956
- Publisher
- John Wiley & Sons Ltd.
- Date published
- 2020
- DOI
- 10.1111/bph.15136
- ISSN
- 1476-5381
- PMID
- 32436225; PMC7429487
- Organisation Unit
- School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99468008302621
- Output Type
- Journal article
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- Domestic collaboration
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- Pharmacology & Pharmacy
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