Denton. Intracerebroventricular infusion of angiotensin II increases water and ethanol intake in rats. Am. J. Physiol. 277 (Regulatory Integrative Comp. Physiol. 46): R162-R172, 1999.-The influence of prolonged ingestion of ethanol on stimulation of water or ethanol intake by intracerebroventricular infusion of ANG II was evaluated in rats. Animals were maintained for 5-6 mo with either 10% ethanol solution or water as their only source of fluid. In both groups of rats, infusion of ANG II

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... a large increase in water intake (7-fold) and a lesser increase in 10% ethanol intake (2-fold). The effect of ANG II on the volume of ethanol solution ingested, however, was inversely related to the concentration of the ethanol solution. As the concentration of ethanol solution was decreased, frequency and duration of drinking bouts increased. The intake of sweetened 10% ethanol solution or commercially produced wine during infusion of ANG II was similar to the intake of 10% ethanol and not related to taste preference. In conclusion, chronic consumption of ethanol solution did not appear to adversely effect ANG II stimulation of water intake. The intake of ethanol solution during infusion of ANG II was inhibited by a direct effect of ingested ethanol and/or by indirect effect from metabolized ethanol. alcohol drinking; drinking behavior; prolonged alcohol intake STUDIES IN HUMANS have shown that the prolonged ingestion of excessive amounts of alcohol may be detrimental to health. Individuals that abuse alcohol or are addicted to alcohol suffer from numerous ailments that may be due to imbalances in body fluid homeostasis (4, 5). As part of our investigation concerned with the effects of prolonged ingestion of ethanol on physiological mechanisms responsible for body fluid and energy homeostasis in mammals, experiments have been conducted on sheep (2) and mice (3) trained to drink ethanol solutions. The animals had access to ethanol solution as their only source of fluid for Ͼ5 mo. This model has the advantage over other models in that very consistent daily levels of ethanol intake are produced. Sheep maintained on 10% ethanol solution had minimal evidence of liver damage and no evidence of any disruption of the thirst mechanism (2). They drank large amounts of water during intracerebroventricular infusion of ANG II, one of the most potent dipsogens known. However, they drank relatively little 10% ethanol solution during intracerebroventricular infusion of ANG II. Similar results were obtained in BALB/c mice (3) , where intracerebroventricular infusion of ANG II caused a substantial increase in water intake but no increase in intake of ethanol solutions. The failure of the intracerebroventricular infusion of ANG II to stimulate intake of ethanol in mice was not due solely to its aversive taste. When given only one fluid to drink, intracerebroventricular infusion of ANG II increased intake of a potassium chloride solution that under free access conditions was shown to have an aversive taste relative to the ethanol solution. Although there have been no studies directly examining the influence of prolonged ethanol intake on thirst mechanisms in rats, evidence consistent with disturbance of these mechanisms has been reported in rats chronically maintained on ethanol (1, 7, 13, 14, 16, 32) . For example, Essig (7) reported that rats chronically maintained with access to 20% ethanol had an exaggerated intake of water when it was made available. Altered sensitivity to vasopressin (32) and altered plasma levels of vasopressin, aldosterone, atrial natriuretic peptide, and brain natriuretic peptide have also been reported (13, 14) . Also, changes in central nervous system mechanisms involved in the regulation of body fluid homeostasis have been observed. Chronic ingestion of ethanol decreases the number of neurons in the supraoptic nucleus (16) and alters the sensitivity of the cholinergic neurons (1). The purpose of the present series of experiments was to evaluate the influence of the prolonged ingestion of ethanol on mechanisms involved in body fluid homeostasis in rats. Specifically, the ability of intracerebroventricular infusion of ANG II to stimulate water intake was determined. In addition, the ability of intracerebroventricular infusion of ANG II to alter ethanol intake was assessed. Although ANG II is a potent stimulus to water intake, its influence on intake of ethanol is controversial. Evidence that intracerebroventricular infusion of ANG II stimulates (8) or does not alter (11) ethanol intake has been reported. The influence of intracerebroventricular infusion of ANG II on intake of solutions of varying ethanol concentration, sweetened ethanol solution and a commercially available wine, was determined to assess the role of flavor factors in modulating the influence of ANG II on fluid intake. METHODS AND RESULTS Animals Preexperimental period. The rats used were male Sprague-Dawley rats, 6-7 wk of age at the start of the preexperimental period. The rats were maintained in sawdust-lined group boxes 70 (length) ϫ 40 (width) ϫ The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.