Homeostatic Origins of Motivation

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DESCRIPTION (provided by applicant): This is a competing renewal application for grant support of research whose general goal is to understand the biological bases of motivated behavior, especially thirst, salt appetite, hunger and satiety. Three series of experiments are proposed. Experiment 1 seeks to determine the early postingestive signals that influence thirst and the secretion of vasopressin (VP) and oxytocin (OT) in rats. In pursuit of this aim, we will determine (a) whether water drinking reduces secretion of VP and OT in response to excitatory stimuli other than that provided by an intravenous NaCl load; (b) whether lesions of area postrema and nucleus tractus solitarius (NTS) blunt the rapid effect of water drinking, or of an intragastric NaCl load, on secretion of VP and OT; and (c) whether maintenance of rats on high-salt diet blunts the rapid inhibitory effect of water drinking on VP and OT secretion. Experiment 2 seeks to determine the excitatory stimuli for thirst during arterial hypotension or hypovolemia, and the inhibitory stimulus for thirst during arterial hypertension. In pursuit of this aim, we will determine (a) whether angiotensin II and neural signals from arterial baroreceptors contribute significantly to thirst during hypotension; (b) whether renal afferent nerves contribute significantly to thirst during hypovolemia in rats with NTS lesions; and (c) whether sinoaortic baroreceptors contribute significantly to the inhibitory effect of arterial hypertension on thirst. Experiment 3 seeks to determine the physiological functions of neurohypophyseal OT secretion in rats given NaCl loads or during arterial hypotension. In pursuit of this aim, we will determine (a) whether OT contributes significantly as a natriuretic hormone when rats are maintained on high-salt diet; and (b) whether OT contributes significantly to secretion of renin during arterial hypotension, and thus to mediation of the induced thirst.