[680] Alcohol Drinker Rats Lower Their Ethanol Intake for One Month after a Single Injection of an Adenoviral Vector Carrying an Antisense Gene for Aldehyde Dehydrogenase Poster Session II: Gene Expression in Animal Model Systems
Nature has developed a protective mechanism against alcohol abuse and alcoholism. In most individuals aldehyde dehydrogenase-2 (ALDH2) readily oxidizes acetaldehyde, a product of ethanol metabolism, allowing excessive alcohol consumption.
In contrast, subjects who carry a point mutation in the ALDH2 gene which lowers aldehyde dehydrogenase activity are strongly protected against alcohol abuse and alcoholism by 66 % to 100 % because of the aversion triggered by the elevation of blood acetaldehyde upon alcohol drinking.
The aim of this study was to mimic such an aversion to ethanol in rats by inhibiting the expression of the Aldh2 gene.
Overall, high acetaldehyde levels and an aversion to ethanol, similar to those experienced by subjects who carry an inactivating mutation of ALDH2, was achieved in rats by the administration of an Aldh2 antisense gene.
These studies open the possibility of developing specific and long-lasting gene based therapies against alcoholism.
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