HOMEOSTATIC ORIGINS OF MOTIVATION

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

DESCRIPTION (Adapted from applicant's abstract): 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. Two series of experiments are proposed to elucidate the central mechanisms by which ingestive behavior is controlled. Experiment 1 aims to determine the brain stem mechanisms by which gastric signals affect ongoing ingestion. In pursuit of this aim, Experiment 1A determines whether rats with surgical lesions of nucleus tractus solitarius (NTS) will overdrink water when thirsty, 10% sucrose solution when hungry, and 0.3 M NaCl when they have a salt appetite, and will do so in the first 10-15 min of the drinking test; Experiment 1B determines whether systemic injection of cholecystokinin (CCK) will inhibit food intake and stimulate pituitary OT secretion in rats with NTS lesions, as it does in rats with lesions of the adjacent area postrema (AP) and in control rats; Experiment 1C determines whether moderate gastric distension will potentiate the anorectic effect of CCK in rats with lesions of AP or NTS and in control rats; and Experiment 1D determines whether CCK pretreatment will eliminate the overdrinking of rats with AP lesions in response to the various stimuli for drinking mentioned in Experiment 1A. Experiment 2 aims to determine the organization of central circuits mediating thirst and NaCl appetite. In pursuit of this aim, Experiment 2A determines the effect of brain lesions produced by intracerebroventricular administration of the plant cytotoxin ricin conjugated to OT (rA-OT) or atrial natriuretic peptide (rA-ANP), treatments which impair the function of brain cells bearing OT or ANP receptors, respectively, on osmotic- and hypovolemia-induced ingestion of water and NaCl solution; Experiment 2B analyzes the cells and functional circuits damaged by rA-OT and rA-ANP treatments; Experiment 2C identifies the brain cells stimulated to express cFos by hypertonic NaCl solution compared to equiosmolar hypertonic mannitol; and Experiment 2D localizes the cells stimulated to express cFos by hypertonic NaC1 solution in rats with rA-ANP induced brain lesions.