Chronic ethanol and pentobarbital administration in the rat: effects on GABAA receptor function and expression in brain.
Chronic exposure of rats to ethanol significantly decrease 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 response 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 alpha-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%). beta-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 alpha-subunit mRNAs in rat cerebral cortex. These data suggest that chronic ethanol exposure alters the level of mRNA's coding for the alpha-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.
Morrow
A L
AL
Section on Molecular Pharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Montpied
P
P
Lingford-Hughes
A
A
Paul
S M
SM
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*
D011963:Receptors, GABA-A; D000431:Ethanol; D010424:Pentobarbital