Differential expression of GABAA receptor subunit mRNAs in ethanol-naive withdrawal seizure resistant (WSR) vs. withdrawal seizure prone (WSP) mouse brain.
Several lines of evidence suggest an important role for ethanol interactions with GABAA receptors in the development of the ethanol withdrawal syndrome. The present study was undertaken to determine whether there is a genetic relationship between ethanol withdrawal seizure severity and the expression of particular GABAA receptor subunits in mouse lines selectively bred for differential sensitivity to ethanol withdrawal seizures. Since GABAA receptor subunit levels are subject to modulation by ethanol, the levels of GABAA receptor alpha 1, alpha 6 and beta 2 subunit mRNAs were measured in cerebellum while alpha 1 and beta 2 subunit levels were determined in cerebral cortex of ethanol-naive WSR and WSP mice. Poly(A)+ RNA was isolated from groups of 6-10 animals and the GABAA receptor subunit mRNA levels were quantified by Northern blot analysis using subunit selective cRNA probes. In the cerebellum, greater levels of each of these subunit mRNAs were detected in WSR1 mice compared to WSP1 mice. The levels of GABAA receptor alpha 1 subunit mRNAs were approximately 26 +/- 16 percent greater for the 4.4 kb transcript and 84 +/- 23 percent greater for the 4.8 kb transcript in WSR mice vs WSP mice. GABAA receptor alpha 6 subunit (2.7 kb) mRNA levels in cerebellum were 159 +/- 58 percent greater in WSR mice than WSP mice, while beta 2 subunit mRNA levels were 110 +/- 30 percent greater in WSR than WSP mice. These results were replicated for the alpha 1 and alpha 6 subunits in WSR2 vs WSP2 mouse cerebella. No differences in beta-actin mRNA levels were detected on the same RNA blots.(ABSTRACT TRUNCATED AT 250 WORDS)
Keir
W J
WJ
Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill 27599.
Morrow
A L
AL
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000096:biosynthesis*; D011963:Receptors, GABA-A / Q000235:genetics*; D012640:Seizures / Q000139:chemically induced* / Q000235:genetics; D013375:Substance Withdrawal Syndrome / Q000235:genetics*
D012333:RNA, Messenger; D011963:Receptors, GABA-A; D000431:Ethanol