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Changes in ethanol effects in knock-in mice expressing ethanol insensitive alpha1 and alpha2 glycine receptor subunits.
San Martin, Loreto S; Armijo-Weingart, Lorena; Gallegos, Scarlet; Araya, Anibal; Homanics, Gregg E; Aguayo, Luis G.
Afiliação
  • San Martin LS; Laboratory of Neurophysiology, Department of Physiology, Universidad de Concepción, Chile; Programa de Neurociencia, Psiquiatría y Salud Mental (NEPSAM), Universidad de Concepción, Chile.
  • Armijo-Weingart L; Laboratory of Neurophysiology, Department of Physiology, Universidad de Concepción, Chile; Programa de Neurociencia, Psiquiatría y Salud Mental (NEPSAM), Universidad de Concepción, Chile.
  • Gallegos S; Laboratory of Neurophysiology, Department of Physiology, Universidad de Concepción, Chile.
  • Araya A; Laboratory of Neurophysiology, Department of Physiology, Universidad de Concepción, Chile.
  • Homanics GE; Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pharmacology & Chemical, University of Pittsburgh, Pittsburgh, PA, USA; Department of Biology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurobiology, Universi
  • Aguayo LG; Laboratory of Neurophysiology, Department of Physiology, Universidad de Concepción, Chile; Programa de Neurociencia, Psiquiatría y Salud Mental (NEPSAM), Universidad de Concepción, Chile. Electronic address: laguayo@udec.cl.
Life Sci ; 348: 122673, 2024 Jul 01.
Article em En | MEDLINE | ID: mdl-38679193
ABSTRACT

AIMS:

Glycine receptors (GlyRs) are potentiated by physiologically relevant concentrations of ethanol, and mutations in the intracellular loop of α1 and α2 subunits reduced the effect of the drug. Knock-in (KI) mice having these individual mutations revealed that α1 and α2 subunits played a role in ethanol-induced sedation and ethanol intake. In this study, we wanted to examine if the effects of stacking both mutations in a 2xKI mouse model (α1/α2) generated by a selective breeding strategy further impacted cellular and behavioral responses to ethanol. MAIN

METHODS:

We used electrophysiological recordings to examine ethanol's effect on GlyRs and evaluated ethanol-induced neuronal activation using c-Fos immunoreactivity and the genetically encoded calcium indicator GCaMP6s in the nucleus accumbens (nAc). We also examined ethanol-induced behavior using open field, loss of the righting response, and drinking in the dark (DID) paradigm. KEY

FINDINGS:

Ethanol did not potentiate GlyRs nor affect neuronal excitability in the nAc from 2xKI. Moreover, ethanol decreased the Ca2+ signal in WT mice, whereas there were no changes in the signal in 2xKI mice. Interestingly, there was an increase in c-Fos baseline in the 2xKI mice in the absence of ethanol. Behavioral assays showed that 2xKI mice recovered faster from a sedative dose of ethanol and had higher ethanol intake on the first test day of the DID test than WT mice. Interestingly, an open-field assay showed that 2xKI mice displayed less anxiety-like behavior than WT mice.

SIGNIFICANCE:

The results indicate that α1 and α2 subunits are biologically relevant targets for regulating sedative effects and ethanol consumption.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Glicina / Etanol / Técnicas de Introdução de Genes Limite: Animals Idioma: En Revista: Life Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Chile País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Glicina / Etanol / Técnicas de Introdução de Genes Limite: Animals Idioma: En Revista: Life Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Chile País de publicação: Holanda