Voluntary alcohol drinking and acetaldehyde metabolism in F2 hybrid crosses of AA and ANA rat lines.
Alcohol-preferring AA and alcohol-avoiding ANA rat lines differ in their acetaldehyde metabolism and this has been suggested to be one reason for their different ethanol drinking behavior. To study whether acetaldehyde accumulation is indeed associated with alcohol drinking behavior and to evaluate which enzymatic differences previously observed in these rat lines are of importance in this regard, we produced an F2 generation from them. ADH and ALDH activities, and ALDH patterns were then assessed from these hybrids and correlated with their voluntary ethanol drinking and blood acetaldehyde concentrations measured during ethanol metabolism. A significant negative correlation between voluntary ethanol intake and blood acetaldehyde concentration was observed in F2 females drinking less than 17% of the total fluid as ethanol. In F2 males, hepatic microsomal high Km ALDH activities correlated negatively with blood acetaldehyde concentrations, indicating that low activity of this isoenzyme in ANA rats could be at least in part responsible for the accumulation of acetaldehyde in their blood. Finally, F2 rats that possessed the cytosolic ALDH isoenzyme pattern most frequently found in the AA rat line drank significantly more ethanol than the animals with typical ANA pattern, suggesting that this polymorphism might also be relevant in the regulation of voluntary ethanol drinking although it is probably not associated with acetaldehyde metabolism.
Koivisto
T
T
Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland.
Eriksson
C J
CJ
D000079:Acetaldehyde / Q000097:blood*; D000428:Alcohol Drinking / Q000097:blood*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D003433:Crosses, Genetic; D003600:Cytosol / Q000201:enzymology; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D016014:Linear Models; D008297:Male; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains; D014836:Volition
D007527:Isoenzymes; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde