The brain controls feeding behavior.If the base of the brain is damaged bilaterally in the ventromedial region of the hypothalamus, rats and other mammals overeat and become tremendously obese (Anand, Dua, & Schoenberg, 1955;Brobeck, Tepperman, & Long, 1943;Wheatley, 1944). Damage in the lateral hypothalamus produces the opposite effect: the animals do not eat and will die in the presence of food and water (Anand & Brobeck, 1951;Anand, Dua, & Schoenberg, 1955). Electrical stimulation through chronically implanted electrodes in the medial hypothalamus suppresses feeding, and stimulation in the lateral hypothalamus elicits it (Brugger, 1943;Larsson, 1954;Wyrwicka & Dobrzecka, 1960).These dramatic and consistent phenomena suggest that a dual hypothalamic mechanism controls food intake. Cessation of eating (satiety) is said to be controlled by a medial

SUMMARY1. When applied directly to the brain, angiotensin II amide, as either the valine5 or isoleucine5 octapeptide, causes rats in normal fluid balance to drink water.2. The drinking response to angiotensin injections is copious, rapid, repeatable within the same test session, and stable over months of testing in the same animal.3. The response is motivationally potent and specific. After injection the animals move directly to the source of water and drink. There is typically no preliminary hyperactivity or subsequent depression. The animals do not eat, gnaw or exhibit other behaviours that are not normally seen during spontaneous drinking. The injections rouse sleeping animals to drink and interrupt eating in animals deprived of food for two days.4. The region of the brain that is most sensitive to angiotensin includes the anterior hypothalamus, the preoptic region, and the septum including the nucleus accumbens.5. Intracranial renin elicited drinking. Bradykinin and vasopressin did not, nor did adrenaline, noradrenaline or aldosterone. In the most sensitive region, sites positive for angiotensin also yielded drinking to carbachol.6. Responses were obtained with 5 ng (ca. 5 p-mole) and occurred reliably with 50 ng angiotensin or more. The dose-response curve for amount drunk rose from 5 to 100 ng and levelled off thereafter. Angiotensin is therefore the most potent dipsogen known and is effective at doses that are reasonably within the concentration range for circulating endogenous angiotensin.

Angiotensin and mineralocorticoids, the hormones of sodium conservation, acted together to arouse a sodium appetite with shorter latency and greater magnitude than is produced by larger amounts of each acting alone. This potentiation was selective for sodium ingestion and occurred in the absence of significant changes in sodium balance. Therefore, because endogenous angiotensin and mineralocorticoids are concurrently elevated during sodium deficiency, sodium appetite may be aroused by a synergy of the peptide and the steroid.

Blockade of central but not peripheral mineralocorticoid receptors, with the antimineralocorticoid RU-28318, reduces but does not suppress salt appetite aroused by sodium depletion in the rat. When central mineralocorticoid blockade is combined with captopril treatment to prevent formation of endogenous angiotensin II the appetite is completely suppressed. Suppression of the appetite occurred without changes in the animals' spontaneous ingestive behaviors, sodium excretion, or insulin-induced food intake. These results demonstrate that a synergy of angiotensin II and aldosterone is responsible for the expression of depletion-induced salt appetite in the rat.

A single sodium depletion enhances the salt appetite that is expressed after a second and subsequent sodium depletions. The enhanced salt intake, as measured by a decrease in latency to drink and an increase in volume of 3% NaCl ingested, is not accounted for by an increased sodium loss. The enhanced salt intake occurs even when the interval between first and second depletion is as long as 4 months. The enhanced salt appetite does not depend on the drinking of salt after the animal's first sodium depletion and is specific for NaCl but not for KCl. Moreover, it can be produced without sodium depletion by the actions of the hormones aldosterone and angiotensin on the brain. These results suggest that angiotensin and aldosterone, which are released in response to sodium depletion, (a) increase renal sodium conservation, (b) evoke a salt appetite to restore the lost sodium, and (c) produce enduring changes in the brain that prepare it for more rapid and more vigorous expression of salt appetite in response to future sodium depletions. Thus the neural mechanisms that govern salt appetite are not only activated by the hormones of sodium conservation but appear also to be organized by them for a lifelong increase in avidity for salty substances.