This application proposes a continuation of my neurobehavioral analysis of pancreatic glucagon's role in the control of postprandial satiety in the rat. The planned experiments are designed, first, to characterize further the behavioral and physiological contexts in which exogenous glucagon controls meal size and elicits postprandial satiety; second, to elucidate the peripheral and central neural mechanisms mediating these effects. The central goal of this project is to advance understanding of the physiological controls of feeding behavior. This is a major problem in behavioral neuroscience, and its solution is a prerequisite for the development of physiologically-based treatments of clinical disorders such as obesity, bulimia, and anorexia nervosa. The investigation of the satiety effect of exogenous pancreatic glucagon is especially relevant in this context because there is evidence that endogenous pancreatic glucagon is necessary for the normal control of meal size in the rat. The proposal has seven purposes: First, to determine the site of action and afferent path to the brain for the satiety effect of exogenous pancreatic glucagon. Second, to determine the sites of the terminals fields in the medulla of the hepatic vagal afferents mediating glucagon's satiety effect. Third, to test whether exogenous glucagon's effects on gastric distention or on rate of gastric emptying mediate glucagon's satiety effect. Fourth, to determine the behavioral characteristics and specificity of the inhibitory effect on feeding of exogenous epinephrine in order to evaluate the hypothesis that epinephrine and glucagon have functionallly identical satiety effects. Fifth, to test the hypothesis that the same peripheral innervation mediates the feeding effects of glucagon and epinephrine. Sixth, to test the hypothesis that hepatic glycogenolysis mediates glucagon's satiety effect by comparing glucagon's potencies to elicit satiety and to elicit glycogenolysis at different times of day. Seventh, to investigate the effect of the intensity of sweet taste on glucagon's satiety effect.
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