Altered Pattern of Na,K-ATPase Activity and mRNA During Chronic Alcohol Consumption by Juvenile and Adolescent Rats

Abstract

The effect of chronic ethanol consumption on cerebral cortical activity of Na,K-ATPase was determined in Long-Evans (LE) rats fed an ethanol-containing diet beginning at different stages of development. Na,K-ATPase activity was operationally resolved into alpha1 and alpha2/3 isozyme activities. There was no significant difference in Na,K-ATPase activities before and after alcohol consumption in the preparations from adult rats. However, for rats beginning alcohol consumption as adolescents, the alpha2/3 activity was significantly elevated following chronic alcohol consumption. Both LE and Sprague-Dawley rats showed this same selective increase in cortical alpha2/3 activity when rats began alcohol consumption as juveniles. The shift in cortical alpha2/3 activity was not observed in cerebellum or subcortical forebrain and was reversible when rats were fed ethanol throughout the normal adolescent period and then withdrawn and tested 2 weeks later (during the adult period). Levels of isoform-specific mRNA were determined in preparations of cerebral cortices of rats showing elevated alpha2/3 isozyme activities. In these preparations, isoform specific alpha2 and alpha3 mRNA was significantly elevated. There was no effect of ethanol feeding on cortical alpha1 mRNA. These findings indicate that the longer term effects of ethanol on the developing brain include elevated Na,K-ATPase activity and a mechanism that is pre-translational and isoform specific.