Comparative analysis of hepatic ethanol metabolism in Fawn-Hooded and Wistar-Kyoto rats.
Results of a number of studies have supported the suggestion that a correlation exists between voluntary ethanol consumption and enhanced ethanol metabolism in some (but not all) rodent strains. However, as yet, the capacity for alcohol-preferring Fawn-Hooded (FH) rats to metabolize ethanol has not been investigated. Hence, the aim of the current study was to compare the activities of the major hepatic enzymes involved in ethanol metabolism--cytosolic alcohol dehydrogenase (ADH) and mitochondrial aldehyde dehydrogenase (ALDH)--in the FH rat and its alcohol-nonpreferring counterpart, the Wistar-Kyoto (WKY) rat. In addition, the effect of chronic (5 weeks in vivo) ethanol pretreatment on the activity of these enzymes was investigated. Alcohol-naive FH rats were found to have significantly higher ADH activity (+61%) and no significant change in ALDH activity when compared with findings for WKY rats. In addition, chronic ethanol self-administration produced a small increase in ADH activity (+14%) in WKY rats only. Taken as a whole, these findings are the first to demonstrate an increased in vitro hepatic ethanol metabolism in alcohol-preferring FH rats and further demonstrate an association between hepatic ethanol metabolism and voluntary ethanol self-administration in rodents.
Lodge
Daniel J
DJ
Department of Pharmacology, Monash University, Box 13E, Clayton, Victoria 3800, Australia. Lodge@BNS.Pitt.edu
Lawrence
Andrew J
AJ
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D002492:Central Nervous System Depressants / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000502:physiology; D051381:Rats; D011921:Rats, Inbred WKY; D013045:Species Specificity
D002492:Central Nervous System Depressants; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase