Universally, researchers agree that peripheral sensory systems play a critical role in the control of meal size. However, they sustain a lively controversy as to the origin of satiety-relevant feedback. Some tend to focus on discrete sources (e.g., the stomach) of potentially-relevant feedback and, as a result, do not address the important issue of integration of intake-inhibitory signals when feedback from disparate sources is concurrently available. This is a serious omission for clinical approaches (both behavioral and pharmacological) to feeding disorders, as well as for nervous system-oriented research into substrates that modulate ingestive behavior as a function of physiological and metabolic variables. In this project the Investigator and his colleagues will undertake a comprehensive analysis of the relative contributions of oral, gastric, and post-gastric signals to the control of nutritive fluid ingestion in the rat. They will provide the first extensive study of the mechanisms that control gastric emptying during ingestion. For this purpose, they will evaluate the effects of: (a) quality and concentration of nutritive fluids ingested, (b) route (oral versus intragastric), rate, and duration of fluid delivery, and (c) complete and selective transections of the subdiaphragmatic vagus nerve, and (d) pharmacological treatment. For the intake studies, the researchers will develop and exploit specialized testing paradigms (intra-oral infusion; drop-size-controlled lickometry) that allow the experimenter to control the parameters of fluid delivery, and the rat to decide when to stop ingesting. This ability to manipulated fluid stimulus delivery facilitates the analysis of gastric emptying during ingestion, and permits the researchers to bring gastric emptying and behavioral results (meal size and duration) into explicit register. To evaluate the relative weightings of feedback from gastric and postgastric sources in the satiation process, the researchers will (a) measure the gastric and postgastric distribution of nutrient at meal's end, and (b) evaluate the effects on meal size and duration of manipulations that systematically bias the rate of gastric fill relative to the rate at which nutrient empties from the stomach. The Investigator expects these experiments to lead to a model for the integrative mechanisms that underlie short-term satiety under normal conditions where oral, gastric, and postgastric receptors are stimulated concurrently.
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