Chronic ethanol and pentobarbital administration in the rat: Effects on GABAA receptor function and expression in brain

A. Leslie Morrow, Pascale Montpied, Anne Lingford-Hughes, Steven M. Paul

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

Chronic exposure of rats to ethanol significantly decreases GABAA receptor-mediated 36Cl- uptake in cerebral cortical synaptoneurosomes. Muscimol and pentobarbital stimulation as well as ethanol enhancement of muscimol-stimulated 36Cl- flux are significantly decreased following chronic ethanol inhalation. Repeated pentobarbital administration has a similar effect on muscimol and pentobarbital-stimulated 36Cl- uptake in cerebral cortical synaptoneurosomes. We have postulated that these adaptive responses may be associated with an alteration of GABAA receptor gene expression. Chronic ethanol exposure resulted in a significant reduction in the levels of GABAA receptor α-subunit mRNA's. The most abundant mRNA species in the rat cerebral cortex were reduced 40-50% (4.4 Kb mRNA, 43%, 4.8 Kb mRNA, 47%) β-Actin mRNA and poly(A)+ RNA levels were not significantly reduced following chronic ethanol exposure. Repeated pentobarbital administration had no effect on the level of the 4.4 and 4.8 Kb transcripts of α-subunit mRNAs in rat cerebral cortex. These data suggest that chronic ethanol exposure alters the level of mRNA's coding for the α-subunit of the GABAA receptor. This decrease may reflect an alteration of mRNA processing in the cell or an alteration in GABAA receptor gene expression.

Original languageEnglish
Pages (from-to)237-244
Number of pages8
JournalAlcohol
Volume7
Issue number3
DOIs
StatePublished - Jan 1 1990
Externally publishedYes

Keywords

  • Cl uptake
  • Ethanol
  • GABA receptor
  • GABA α-subunit mRNA
  • Pentobarbital

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