Recent evidence from our laboratory and others has proven our 1973 hypothesis that cholecystokinin (CCK) released from the small intestine by the preabsorptive stimuli of ingested food is part of the negative feedback, satiating information that acts to terminate eating and control meal size. Thus, CCK is the first endogenous, short-term satiating signal to achieve physiological status. Four of the five specific aims of this proposal are concerned with aspects of the satiating effect of peripheral CCK that are not understood. These are (1) the mode of action of CCK (endocrine or paracrine); (2) the role of receptors for CCK on gastric vagal afferent fibers in mediating the peripheral effect of CCK to the brain where it is processed into information to stop eating; (3) the hormonal basis for the reported, decreased satiating potency of peripherally administered CCK in female rats compared to male rats; and (4) the site of serotonin (5-HT) receptor mechanism in the brain that is sufficient to account for the reversal of the satiating effect of peripheral CCK by 5-HT antagonists. The fifth specific aim is concerned with investigating the interaction between CCK in the brain and CCK and other peripheral satiating mechanisms in the satiating effect of postingestive food stimuli. The effects of all experiment treatments will be measured by both interval intakes and a new microstructural analysis of electronic lickometer records that permits estimates of the moment-by- moment interaction of the positive (stimulating) and negative (satiating) feedback effects of ingested food and specific treatments during a meal. Better understanding of these problems will provide fundamental information about the biological mechanisms that control meal size and stop eating. The results will also provide potential pharmacological targets for new treatments of binge eating that occurs in bulimia and some forms of obesity and seeks a biological basis for the much higher incidence of binge eating reported in women than in men.
Showing the most recent 10 out of 51 publications
