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1. When applied directly to the brain, angiotensin II amide, as either the valine5 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.
7. Injections into the sensitive region of doses of angiotensin that were effective for drinking did not produce peripheral haemodynamic changes in lightly anaesthetized rats.
8. This work strengthens the suggestion that angiotensin is a natural hormone of drinking behaviour that participates in extracellular thirst by its release from the kidney and subsequent direct action on a specific chemoreceptive region in the anterior diencephalon and limbic lobe.
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