This proposal is designed to analyze the sites and mechanisms of the effect of food stimuli acting primarily preabsorptively on meal size in normal rats, in rats with ventromedial hypothalamic obesity (VMH), and in Zucker (fa/fa) rats with genetic obesity. The major aim of the proposal is to attempt to measure as independently as possible the stimulating and satiating effect of food stimuli on eating. This will be done by exploiting the apparent differential localization of these effects along the gut -- the mouth is the predominant site for the stimulating effect, and the stomach, small intestinal and liver are the predominant sites for the satiating effect. This analysis is facilitated by using the sham-feeding rat preparation and techniques for restricting food stimuli to the stomach or small intestine. The food stimuli are sucrose and fat in the form of corn oil; these foods stimulate eating in normal rats and even more so in VMH rats and are reported to do so in human eating disorders, particularly in bulimia. The major mechanism investigated for the stimulating effect of food is the central dopamine system; the major mechanism investigated for the satiating effect is the vagus nerve, especially its afferent fibers. There are three specific aims: 1. Investigate the stimulating and satiating effects of sucrose and corn oil on eating as a function of sex, interval of food deprivation, and photoperiod in normal, VMH, and fa/fa rats. 2. Investigate the effect of selective afferent and efferent vagotomy on the stimulating and satiating effects of sucrose and corn oil on eating in normal, VMH, and fa/fa rats. 3. Investigate the hypothesis that central dopaminergic mechanisms mediate a significant part of the stimulating (positive reinforcing) effect of sucrose and corn oil during sham feeding in normal, VMH and fa/fa rats.
