Previously it was demonstrated that digitalis-like cardiotonic steroid, marinobufagenin (MBG), is implicated in the development of ethanol addiction in rats. We hypothesized that (i) levels of sodium pump ligand, MBG, would be negatively correlated with the amount of ethanol consumed by rats, and (ii) that spironolactone would oppose the MBG induced ethanol-seeking behavior and blood pressure in rats.Voluntary consumption of 9% alcohol (vs. water) during 10 days period by 11 adult male Wistar rats was studied. Eight weeks after the beginning of the experiment, the animals were divided into two treatment subgroups: high alcohol drinkers (HAD, n=6, daily consumption of ethanol > 4 g/kg) and low alcohol drinkers (LAD, n=5, daily consumption of ethanol < 4 g/kg) rats. Spironolactone treatment (7 days) was started following 3-day habituation to intragastric vehicle administration. Consumption of ethanol and blood pressure were recorded daily.Urinary MBG excretion at baseline was 11.2±0.6 pmoles in HAD rats and 19.1±2.9 pmoles (p<0.05) in LAD rats, respectively. Seven days of spironolactone treatment was associated with reduction in ethanol intake (2.9 g/kg/24 hr), reduction in systolic blood pressure (5 mm Hg), and increase in sodium excretion (1 mmol/24 hr).Levels of MBG may be a predisposing factor to voluntary ethanol intake. Spironolactone, along with antihypertensive effect, decreases ethanol intake.