HOMEOSTATIC ORIGINS OF MOTIVATION

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This is a competing continuation application for grant support of research whose general goal is to understand the biological bases of motivated behavior, especially thirst, sodium appetite, hunger and satiety, and the complementary physioligcal contributions to homeostasis. The concept of motivation refers to the urge to seek, obtain and consume food or drink. It is traditional to consider need as the basis for this urge. Sodium appetite and thirst do reflect such a need; in both cases excitratory stimuli seem to promote ingestion and inhibitory stimuli terminate it. In contrast, with food intake we are focsussing on inhibitory stimuli because specific excitartroy stimuli do not seem to exist. Recent research has suggested that activity in oxytocinergic neurons projecting centrally from the paraventricular necleus (PVN), reflected in pituitary oxytocin (OT) secretion, associated with the inhibition of food and NaCl ingestion in rats. Six series of experiments are proposed to test this hypothesis. The role of several enteric peptide hormones, including cholecytokinin, bombesin, and insulin, in the inhibition of food intake in rats is the focus of Experiment 1. Gastric distention may be another important inhibitory stimulus in this regard, and Experiment 1 also examines the effects on gastric emptying in rats of various treatments known to reduce food intake. The effects of destroying PVN, or the noradrenergic and serotonergic afferents to PVN, on OT secretion of rats in response to nausea-producing agents is the focus of Experiment 2. Experiment 3 examines the role of the central vasopressinergic neurons in the control of food intake in human subjects. Experiment 4 determines whether induced alterations in OT secretion parallel the effects of various treatments known to affect NaCl ingestion in rats. Experiment 5 determines whether in various models of sodium appetite in rats, the stimulation of OT secretion by NaCl consumption is blunted. Experiment 6A examines the effects on sodium appetite of destroying PVN, or the monoaminergic afferents to PVN. Finally, Experiment 6B examines interactions in the controls of food and NaCl ingestion in rats by determining the effects of nausea- producing agents and putative satiety agents on sodium appetite, and the effects of osmotic stimuli to OT secretion on food intake.