The long term goals of this work are to identify the neuronal systems through which peptides influence food intake, to characterize these systems both anatomically and functionally, and ultimately to appreciate how peptides and the neurons that mediate their actions participate in physiologically and/or pathologically-induced changes in food intake. The Principal Investigator (PI) has concentrated on neural systems that mediate suppression of food intake by cholecystokinin (CCK), a peptide found in the intestine and in the brain. He has found that CCK mediates reductions of food intake that occur when some nutrients are placed in the small intestine. The proposed experiments are designed to determine where the CCK that mediates reduction of food intake acts and at what type of receptors it acts. To accomplish these ends the experiments address the three following specific aims: 1) use pharmacological and immunological methods together with restricted drug application to identify the general location and subtype of the CCK receptors involved in suppression of sham feeding by intestinal nutrients; 2) utilize intraintestinal infusions of agents that desensitize gut neurons to assess the role of the local intestinal innervation in suppression of food intake by intestinal nutrients and exogenous CCK; and 3) use immuno-histochemical techniques to anatomically identify central and peripheral neurons that are activated by intestinal stimuli and exogenous peptides.
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