TITLE

Reduction of Ethanol Consumption in Alcohol-Preferring Rats by Dual Expression Gene Transfer

AUTHOR(S)
Rivera-Meza, Mario; Quintanilla, María Elena; Tampier, Lutske
PUB. DATE
March 2012
SOURCE
Alcohol & Alcoholism;Mar/Apr2012, Vol. 47 Issue 2, p102
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Aims: To mimic, in an animal model of alcoholism, the protective phenotype against alcohol consumption observed in humans carrying a fast alcohol dehydrogenase (ADH1B*2) and an inactive aldehyde dehydrogenase (ALDH2*2). Methods: We developed a multiple expression cassette adenoviral vector (AdV-ADH/asALDH2) encoding both a fast rat ADH and an antisense RNA against rat ALDH2. A control adenoviral vector (AdV-C) containing intronic non-coding DNA was also developed. These adenoviral vectors were administered intravenously to rats bred as high alcohol-drinkers (University of Chile bibulous) that were previously rendered alcohol dependent by a 75-day period of voluntary 10% ethanol intake. Results: Animals administered AdV-ADH/asALDH2 showed a 176% increase in liver ADH activity, whereas liver ALDH2 activity was reduced by 24%, and upon the administration of a dose of ethanol (1 g/kg, i.p.), these showed arterial acetaldehyde levels that were 400% higher than those of animals administered AdV-C. Rats that received the AdV-ADH/asALDH2 vector reduced by 60% their voluntary ethanol intake versus controls. Conclusion: This study provides evidence that the simultaneous increase of liver ADH and a reduction of ALDH activity by gene transfer could constitute a potential therapeutic strategy for the treatment of alcoholism.
ACCESSION #
72441760

 

Related Articles

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics