GABA(A) receptor β2 subunit mRNA content is differentially regulated in ethanol-dependent DBA/2J and C57BL/6J mice

Matthew T. Reilly, Kari J. Buck

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Chronic ethanol treatment is known to alter gene expression and function of γ-aminobutyric acid type-A (GABA(A)) receptors. Here we focus on the β2 subunit which is widely expressed in the mammalian brain, and plays a key role in the GABA binding site. Previous studies using rodent models of ethanol dependence show either increased or no change of β2 subunit mRNA and peptide content following chronic ethanol administration. In humans, polymorphism at the β2 subunit is associated with ethanol dependence in some, but not all, populations. In the present study we measured mRNA content in the cerebellum and cerebral cortex using ethanol-naive and ethanol-dependent DBA/2J and C57BL/6J mice. The DBA/2J strain displays severe ethanol withdrawal severity, while the C57BL/6J strain shows milder withdrawal reactions. RNase protection analysis demonstrated that the DBA/2J strain is more sensitive to ethanol-induced increases in β2 subunit mRNA content in the cerebellum, showing significant increases at lower blood ethanol concentrations than C57BL/6J mice. The ethanol-induced regulation in C57BL/6J mice appears to be more complex, with decreases in β2 subunit mRNA content at low blood ethanol concentrations, and increases at higher concentrations. These data suggest that differences between C57BL/6J and DBA/2J mice in the degree of physical dependence (withdrawal) on ethanol may be related to differential sensitivity to ethanol regulation of β2 subunit expression. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)443-452
Number of pages10
JournalNeurochemistry International
Volume37
Issue number5-6
DOIs
StatePublished - Nov 1 2000

Keywords

  • Alcohol
  • Gene expression
  • Inbred mouse strains
  • Pharmacogenetics

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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