Bombesin (BN)-like peptides, which include gastrin releasing peptide (GRP) and neuromedin-B (NMB), are recognized as significant neuroregulatory peptides. Their bioactivities range from acting as growth factors in both normal cellular proliferation and pathogenesis, to regulating energy metabolism. BN-like peptides are implicated in the physiological control of food intake. Previous work from this laboratory has shown that caudal brainstem (CBS) systems are sufficient to mediate the behavior-controlling effects of BN-like peptides. The CBS pharmacological system that mediates the action of systemic and central injections of BN-like peptides on feeding has yet to be specified. Central administration of potent GRP preferring receptor antagonists will be used to suggest the pharmacological mechanism and BN receptor subtype by which the central effects of BN-like peptides are exerted after systemic and central BN injections. The neural mechanisms that control the effects of BN on behavior remain largely undefined. Within the CBS, several lines of evidence indicated that BN-like peptides may exert their behavioral actions through the nucleus of the solitary tract (NST). Whether the reduction in feeding produced by intra-NST injections of BN has any relationship to the physiological control of feeding will be pursued by determining the behavioral and anatomical specificity of the injection effects. The effects of BN on feeding may be mediated by the projections of the NST to CBS nuclei, such as the caudal NST, area postrema (AP), and parabrachial nucleus (PBN). The functional participation of these nuclei will be identified by investigating whether lesions (electrolytic and ibotenic acid) of these sites have specific effects on the anorexia produced by central and peripheral BN administration. The results will serve to identify the CBS neural circuit that mediates the actions of BN-like peptides on feeding. Behaviorally effective caudal brainstem BN injection sites are in close proximity to feeding-related trigeminal and gustatory projections. Experiments will investigate whether systemic and intra-CBS injections of BN modify the sensitivity of specific sensory systems. The results will provide mechanistic answers to questions of how BN affects behavior. Collectively, the results will identify the pharmacological, neuroanatomical, and sensory system that mediate the effects of BN-like peptides on feeding and behavior.
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