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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37MH025140-19
Application #
3486383
Study Section
Special Emphasis Panel (NSS)
Project Start
1979-06-01
Project End
1997-05-31
Budget Start
1992-06-01
Budget End
1993-05-31
Support Year
19
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Arts and Sciences
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Smith, Carrie A; Curtis, Kathleen S; Smith, James C et al. (2007) Presystemic influences on thirst, salt appetite, and vasopressin secretion in the hypovolemic rat. Am J Physiol Regul Integr Comp Physiol 292:R2089-99
Stricker, Edward M; Hoffmann, Myriam L (2007) Presystemic signals in the control of thirst, salt appetite, and vasopressin secretion. Physiol Behav 91:404-12
Stricker, Edward M; Bushey, Michael A; Hoffmann, Myriam L et al. (2007) Inhibition of NaCl appetite when DOCA-treated rats drink saline. Am J Physiol Regul Integr Comp Physiol 292:R652-62
Hoffmann, Myriam L; DenBleyker, Megan; Smith, James C et al. (2006) Inhibition of thirst when dehydrated rats drink water or saline. Am J Physiol Regul Integr Comp Physiol 290:R1199-207
Manesh, Reza; Hoffmann, Myriam L; Stricker, Edward M (2006) Water ingestion by rats fed a high-salt diet may be mediated, in part, by visceral osmoreceptors. Am J Physiol Regul Integr Comp Physiol 290:R1742-9
Stricker, Edward M; Hoffmann, Myriam L; Riccardi, Christiana J et al. (2003) Increased water intake by rats maintained on high NaCl diet: analysis of ingestive behavior. Physiol Behav 79:621-31
Stocker, Sean D; Smith, Carrie A; Kimbrough, Celeste M et al. (2003) Elevated dietary salt suppresses renin secretion but not thirst evoked by arterial hypotension in rats. Am J Physiol Regul Integr Comp Physiol 284:R1521-8
Stricker, Edward M; Sved, Alan F (2002) Controls of vasopressin secretion and thirst: similarities and dissimilarities in signals. Physiol Behav 77:731-6
Stocker, Sean D; Stricker, Edward M; Sved, Alan F (2002) Arterial baroreceptors mediate the inhibitory effect of acute increases in arterial blood pressure on thirst. Am J Physiol Regul Integr Comp Physiol 282:R1718-29
Stricker, Edward M; Callahan, John B; Huang, Wan et al. (2002) Early osmoregulatory stimulation of neurohypophyseal hormone secretion and thirst after gastric NaCl loads. Am J Physiol Regul Integr Comp Physiol 282:R1710-7

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