This application proposes investigations of the role of the ovarian hormone estradiol in feeding and bodyweight in female rats. Sexual differentiation in the physiological controls of eating may contribute to the increased vulnerability of women to anorexia nervosa, bulimia nervosa, and some forms of obesity or exacerbate the course of these disorders. Furthermore, disordered meal size is the crucial behavioral change in eating disorders, including the binge eating of obesity, and estradiol potently controls meal size in animals by tonically and phasically increasing the satiating potency of food. Therefore, this application proposes to determine the peripheral and central mechanisms through which estradiol modulates the satiating potencies of gastric and intestinal food stimuli that are known physiological controls of meal size. State-of-the-art behavioral, physiological, and molecular techniques are used. There are eight specific aims: (1) Determine whether estradiol tonically or phasically increases gastric satiation, using rats with inflatable pyloric cuffs. (2) Determine whether estradiol tonically or phasically increases intestinal satiation using duodenal nutrient infusions. (3) Determine whether estradiol receptors in the nucleus tractus solitarius and adjacent caudal brainstem are sufficient for the estrogenic control of feeding by testing the effects of microinjecitons of estradiol directly into the caudal brainstem; (4) Identify brain areas in which increases in neuronal activity, as measured by quantitative c-Fos immunocytochemistry, accompany tonic or phasic estrogenic increases in gastric or intestinal satiation. (5) Determine cellular sites of initiation of the tonic and phasic estrogenic controls of meal size by identifying cellular co-localization of feeding-elicited c-Fos expression and estradiol receptor-alpha expression. (6) Determine the necessity of abdominal vagal and splanchnic afferents in the tonic and phasic estrogenic controls of meal size in rats with selective abdominal afferent denervations. (7) Determine the tonic and phasic effects of estradiol on the neurophysiological responses of single vagal afferent fibers to meal-related food stimuli. (8) Determine the tonic and phasic effects of estradiol on glutamate synaptogenesis in the brainstem by using immunocytochemical detection of synaptic proteins. [unreadable] [unreadable]
NIH ExPorter
NIH ExPorter