This project is an investigation of the interaction between ethanol, norepinephrine and Na plus, K plus Adenosine triphosphatase (Na plus, K plus ATPase), the molecular basis of active cation transport. These studies will test the hypothesis that ethanol acts in part by blocking the stimulation of Na plus, K plus ATPase by norepinephrine, and that an abnormality in regulation of Na plus, K plus ATPase may provide a biochemical marker for susceptibility to alcoholism in man. Studies will include ethanol effects on rat brain, human red blood cells, postmortem human brain tissue. Studies in rat brain will focus on interactions between ethanol and norepinephrine in Na plus, K plus ATPase regulatin and on effects of acute and chronic ethanol on the stimulation of Na plus, K plus ATPase by norepinephrine in vivo, on regulation of Na plus, K plus ATPase, and on noradrenergic metabolites and receptor binding. These experiments will also examine effects on a recently discovered endogenous inhibitor of Na plus, K plus ATPase. Studies in human red blood cells will use cells from patients newly admitted to an inpatient alcohol treatment unit, the same patients after being drug-free for four weeks, and age- and six-matched comparison subjects. Na plus, K plus ATPase activity, its sensitivity to ethanol in vitro, and levels of an sensitivity to the endogenous inhibitor of Na plus, K plus ATPase will be examined. Similar studies, in addition to examination of sensitivity to norepinephrine and levels of nerve-specific ATPase, will be carried out in postmortem brain tissue.