The aim of this project is to provide an understanding of the mechanisms underlying the phenomenon of inadequate thirst in elderly people, and their resultant failure to fully correct states of dehydration. First, we are developing and characterizing an anima (rat) model for aging deficits in thirst and sodium appetite, using two strains of rats and both males and females tested up to 20 months of age. These rats will be tested on a battery of tests of thirst and sodium appetite, using both natural and pharmacological stimulants, designed to engage and thus probe selected known mechanisms of these behaviors. In parallel with the behavioral studies, the mechanism of the deficits will be examined, using measurements of various plasma hormones and brain peptide receptors. On the basis of preliminary findings, we are focusing particular attention on the responsiveness of components of the renin-angiotensin-aldosterone system as a function of age. Angiotensin will be administered both centrally and peripherally in thirst studies, and receptors for angiotensin will be measured in the diencephalon and in the adrenal gland. Studies of salt intake will employ both angiotensin and mineralocorticoid-related stimuli of salt appetite. Spontaneous preference for NaCl will be determined. The effect of age on the temporal relationship of eating and drinking will be examined under both baseline conditions and during a switch of hydrationally-demanding diet. This will examine the flexibility of learned spontaneous drinking patterns in aging.
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