Alterations in heart and liver metabolism were determined periodically in Sprague-Dawley rats pair-fed a liquid diet (ethanol, 36% of calories) for times as long as 1 year. In liver mitochondria the rate of ATP synthesis was lowered significantly after ethanol administration for 1 month and longer feeding periods. In liver microsomes from ethanol-fed animals, ethanol oxidation and aniline hydroxylation increased 1.5- and 3.5-fold, respectively, after 1 month and remained elevated at the longer feeding intervals. Electron microscopic analyses of heart left ventricles revealed no alterations from ethanol consumption for 1 month. Alterations including disrupted mitochondrial cristae, dilatation of sarcoplasmic reticulum, and widening of the intercalated discs were observed after 6.5-month feeding periods. Myocardial concentrations of creatine, creatine phosphate, ATP, ADP, and Pi remained constant even after ethanol consumption for 9 months. After a 12-month feeding period slight changes in cardiac mitochondrial energy-linked properties were observed which were not as pronounced as those occurring in liver mitochondria. The activity and oligomycin sensitivity of the ATPase were not altered in cardiac mitochondria, whereas in liver preparations significant alterations in these properties of the ATPase were apparent after ethanol consumption for 1 month and the longer feeding periods. These observations suggest that the liver responds more quickly and dramatically to chronic ethanol consumption than does the heart.

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Free-choice consumption of alcohol by mice with differing phenotypic alcohol preferences caused uniformly large decreases in brain cyclic AMP-dependent protein kinase activity toward an exogenous substrate (histone 2b) but the effect of alcohol on brain cyclic AMP binding activity was strain-specific. Furthermore, particulate kinase phosphorylating activity toward an endogenous protein (kinase regulatory subunit, RII) was altered by alcohol consumption in a strain-specific manner. The changes in cyclic AMP binding and phosphorylating activity appeared to result from phenotypic differences in the brain's response to alcohol. Thus, low preference animals were sensitive to alcohol and showed a large decrease in cyclic AMP binding and an increase in phosphorylation of regulatory subunit in response to alcohol. In contrast, high preference strain had only a small decrease in cyclic AMP binding and a decrease in phosphorylation, even though these animals consumed a significantly larger dose of alcohol. These data suggest that changes in cyclic AMP binding and/or phosphorylation of kinase regulatory subunit may be phenotypic markers of alcohol preference in inbred mice.