Evidence supports a role of gut and brain peptides, functioning as neurotransmitters and neuromodulators, in the control of energy homeostatic responses. Bombesin (BBS) is one such peptide and high concentrations of BBS binding sites are present in the gastrointestinal tract and caudal brainstem (CBS). Furthermore, converging lines of evidence support the notion that BBS participates in normal satiation. The effects of BBS injection on feeding appear to mediated via both ascending visceral afferent signals and this direct action on brain sites. Recent reports from this lab indicate that the caudal brainstem is a site where humoral BBS acts to inhibit feeding. This application describes experiments that will examine the physiological role of brainstem BBS in the control of food intake and satiety, the neural and sensory mechanisms that mediate 4th ventricle bombesin's effect on food intake, and the CBS sites of BBS action. First, what is the functional relationship between 4th icv BBS and peripheral peptide injection (cholecystokinin (CCK8), BBS) effects on feeding? Measurements of food intake following combined 4th icv BBS and systemic BBS and CCK injections will indicate if these signals interact (synergistically or additively) or activate independent neural systems. An interaction would provide evidence for a gut- brainstem peptide axis in the control of food intake. Second, the relationship between BBS-elicited afferent signals originating in the CBS and other levels of the neuraxis and periphery will be examined. Results obtained from decerebrate rats and rats with peripheral efferent denervation will show whether 4th icv BBS injection effects are mediated by neural interactions with forebrain and/or peripheral sites. Third, direct injections of BBS into CBS areas with high concentrations of BBS binding sites will demonstrate the functional significance of these sites in the control of food intake. Last, the sensory consequences (satiety, malaise) of 4th icv BBS injection will be inferred by measuring the behavioral specificity of 4th icv bombesin's inhibitory effects and whether rats developed a taste aversion to stimuli associated with 4th icv BBS injection. When taken together, the results will demonstrate the functional significance of CBS injection. When taken together, the results will demonstrate the functional significance of CBS afferent signals elicited by BBS in the control of food intake. The information gained will further decipher the organization of ingestive behavior and gut-brain peptide interactions in the control of energy homeostasis.
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