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Aldehyde Dehydrogenase 2 Anti-Sense in the Ventral Tegmental Area Reduces Alcohol Drinking

Ivan Diamond, Peidong Fan, Maria P Arolfo and Lina Yao

We have reported that aldehyde dehydrogenase 2 (ALDH2) inhibitors suppress alcohol seeking and drinking in rats even in the absence of alcohol and acetaldehyde. These behavioural changes suggest that ALDH2 in brain could be a target for ANS-6637 inhibition to suppress alcohol seeking and drinking. Here we ask whether ALDH2-RNA anti-sense administered directly into the Ventral Tegmental Area (VTA) also reduces alcohol drinking.

A recombinant adenoviral vector expressing rat AGS3 and specific RNA antisense against ALDH2 was injected into the VTA of actively drinking alcohol-preferring (iP) rats in a 2-bottle choice study with 10% alcohol (v/v) and water. Controls received scrambled RNA. Alcohol consumption was assayed before and after adenoviral injection. Histology confirmed cannulae implantation.