Chronic ethanol treatment alters brain levels of γ-aminobutyric acidA receptor subunit mRNAs: Relationship to genetic differences in ethanol withdrawal seizure severity

Kari Buck, Lisa Hahner, James Sikela, R. Adron Harris

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Chronic ethanol treatment is known to alter the function of the γ-aminobutyric acidA (GABAA) benzodiazepine receptor complex. To determine if genetic differences in development of ethanol dependence are related to expression of GABAA receptor subunits, we measured whole brain levels of mRNA for the α1 α3, α6, γ2s, γ2L, and 73 receptor subunits in withdrawal seizure-prone and -resistant (WSP and WSR, respectively) mice fed an ethanolcontaning liquid diet or a control diet. Brain poly(A)+ RNA was converted to cDNA and amplified by the polymerase chain reaction using primers conserved among GABAA receptor subunits. Quantification was carried out by densitometric analysis of Southern blots generated using subunit-specific probes. Chronic ethanol treatment decreased the content of α1 mRNA in WSP but not WSR mice and decreased the content of α6 mRNA in WSR but not WSP mice. The content of γ3 mRNA was increased by chronic ethanol in both lines. In untreated mice, the WSP line had lower levels of α3 and α6 mRNA than the WSR line. Thus, a decrease in the content of α1 mRNA is most clearly linked with development of withdrawal signs, although the amounts of α6 and α3 may also be important in the genetic differences between WSP and WSR mice. In contrast, levels of mRNA for γ2s and γ2L subunits do not appear to be altered in ethanol dependence.

Original languageEnglish (US)
Pages (from-to)1452-1455
Number of pages4
JournalJournal of Neurochemistry
Volume57
Issue number4
Publication statusPublished - Oct 1991

    Fingerprint

Keywords

  • γ-Aminobutyric acid
  • γ-Aminobutyric acid receptor subunits
  • Alcohol dependence
  • Benzodiazepines
  • Ethanol
  • Genetics
  • Polymerase chain reaction
  • Seizures

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this