Understanding the role of the nervous system in feeding control is an important goal for basic and clinical science. In humans, the excessive feeding associated with some obesities increases the probability of diabetes, hypertension, and heart disease. Other feeding-related problems (failure to thrive, early satiety, dyspepsia, gastroesophageal reflux, dysphagia, cachexia, anorexia, bulimia) account for a significant portion of health-care expenditures in the U.S.. Clearly, basic research into the location and operating characteristics of the neural substrates that control feeding behavior is essential for: an understanding of the basic physiology of intake control, an appreciation of the CNS underpinnings of various feeding pathologies, and the development of effective pharmacological treatments. We believe, as did Sherrington that the most fruitful approach to analyzing a complex distributed neural control system, such as that controlling feeding behavior, begins at the anatomical level(s) of the relevant sensory inputs and motor outputs. It is a given that many of the relevant sensory inputs (taste, visceral) enter, and all of the consummatory motor outputs (somatic and autonomic) emerge, at the level of the caudal brainstem (CBS). To address the issue of integration, we developed a chronic decerebrate rat (CD) model and have provided data that call attention to a CBS contribution to intake control. When the CD and intact rat respond similarly to selective treatments we can infer that the CBS-- neurally disconnected from the hypothalamus long held to be the seat of intake control-- is sufficient for all elements of the integrated response. In addition, with 4th icv infusion of orexigenic agents we will explore the relevance of CBS receptor systems to the integrated behavioral response of the neurologically intact rat. Finally, we approach a more anatomically resolved analysis of the intake-relevance of specific CBS structures through intraparenchymal infusion, cFos immunohistochemical, and NPY mRNA expression studies. The proposed experiments address the following specific aims evaluate: (1) the sufficiency of the CBS for response to signals that underlie short-term intake control; (2) the role of CBS structures in long-term intake control and (3) the relevance of CBS receptors to the feeding response evoked by selected orexigenic agents.
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