Document Detail


The cerebellar GABAA alpha6 subunit is differentially modulated by chronic ethanol exposure in normal (R100R) and mutated (Q100Q) sNP rats.
MedLine Citation:
PMID:  14751585     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sardinian alcohol non-preferring (sNP) rats carry a point mutation (R100Q) in the cerebellar expressed GABAA receptor alpha6 subunit gene, leading to a higher sensitivity to ethanol and diazepam. The role of the alpha6 subunit gene cluster in the ethanol non-preferring phenotype was here investigated by measuring the levels of alpha1, alpha6 and gamma2 peptide in the cerebellum of normal (RR) and mutated (QQ) sNP rats after 2 weeks of chronic ethanol administration. Western blot analysis revealed that the alpha6 subunit is increased in RR sNP rats after chronic ethanol exposure (25.44%+/-8.69 versus control), while it remained unchanged in mutated QQ sNP rats. Interestingly, chronic ethanol administration decreased alpha1 peptide levels in the cerebellum of both rat lines to a similar extent (30.99%+/-6.74 and 27.12%+/-9.83 in RR and QQ rats, respectively), while gamma2 peptide levels remained unchanged. To further correlate the genetic and biochemical difference of the normal and mutated sNP rats with their aversive phenotype, we exposed sNP rats to a protocol of acquisition and maintenance of ethanol drinking. QQ sNP rats drank less ethanol than RR rats during the acquisition phase, but such difference was lost during the maintenance phase. These data may contribute to elucidating the mechanisms of alcohol avoidance in rat lines selected for this behavior when exposed to ethanol solution.
Authors:
Angela Sanna; Elena Congeddu; Luisella Saba; Anna Porcella; Giorgio Marchese; Stefania Ruiu; Paola Casti; Pierluigi Saba; Luca Pani
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Brain research     Volume:  998     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-30     Completed Date:  2004-04-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  148-54     Citation Subset:  IM    
Affiliation:
Molecular Biology, Neuroscienze S.c.a r.l., Via Palabanda 9, I-09123 Cagliari, Italy. mangela.sanna@ms.crs4.it
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MeSH Terms
Descriptor/Qualifier:
Alcoholism / genetics*
Animals
Blotting, Western
Cerebellum / drug effects*,  metabolism
Ethanol / pharmacology*
Mutation
Rats
Rats, Mutant Strains
Receptors, GABA-A / drug effects*,  genetics*
Chemical
Reg. No./Substance:
0/Receptors, GABA-A; 64-17-5/Ethanol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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