Karen Ackroff - US grants

The studies proposed in this application are designed to bridge the gap between the two general approaches to animal feeding behavior. The homeostatic approach emphasizes animals' responses to a variety of internal cues, while the ecological approach has sought explanations for animals' patterns of food intake in external factors, such as foraging cost and food availability. Because these models were developed by and remain largely segregated within different scientific disciplines, little is known about the interaction of physiological and environmental determinants of feeding behavior. A third approach, which emphasizes the hedonic aspects of eating, is also poorly integrated into the homeostatic and ecological models. The general goal of the proposed studies is to combine these areas of investigation, by asking whether psychobiological controls of food intake already identified in free-feeding animals have the same effects when ecological constraints also operate. The specific aims are to compare the responsiveness of foraging and free-feeding animals to a variety of previously identified internal and external signals that initiate meals and cues that maintain feeding, and to compare their ability to adjust protein intake in response to internal changes in nutritional state. Foraging animals' regulation of food intake suggests that the animals' responsiveness to internal signals for meal initiation and termination is modified by the external demand of meal cost. As the cost of obtaining meals increases, foragers eat fewer meals per day and increase average meal size, keeping total intake constant over a range of food-access costs. The proposed studies will combine several well-developed technologies. In the laboratory simulation of foraging, animals will be required to work for access to meals and their behavior will be compared to that of animals given free access to meals. Intragastric infusion techniques will allow the separation of oral and postingestive stimuli for the study of palatability, nutrient density and quality. The examination of physiological signals will make use of on-line blood glucose recording and automated infusions of cholecystokinin, so that freely behaving animals can be studied with minimal disturbance by handling. Exteroceptive stimuli will be used to elicit conditioned meal initiation and to signal impending food restriction. Computerized data collection and control will allow the continuous monitoring of all foraging and feeding behavior. This research, which involves the fields of psychology, biology and nutrition, will provide new information on the interaction of internal physiological cues and external environmental cues in the control of caloric intake and nutrient selection under free-feeding and simulated foraging conditions.

This project will investigate the appetite for alcohol from a nutrient-conditioning perspective. The potent pharmacological actions of alcohol in reinforcing many forms of behavior have been extensively investigated. Less is known about alcohol as a nutrient, particularly about its nutritionally-based reinforcing actions. Recent animal studies demonstrate that nutrients (carbohydrate, fat, protein) have positive (reinforcing) positingestive consequences that influence food choice and consumption by conditioning flavor preferences and acceptance. These preferences can be remarkably strong and persistent. Animals also learn to prefer flavors associated with the postingestive actions of alcohol at moderate doses, although at higher doses aversions rather than preferences may develop. The potency of alcohol as a reinforcer may result because it has both nutritive and pharmacological reinforcing actions. The specific aims of this project are to 1) evaluate the effectiveness of ethanol in conditioning flavor preferences using a variety of protocols; 2) evaluate the orosensory conditioned stimulus (flavor) in ethanol-conditioned preferences; and 3) compare the postingestive reinforcing effects of ethanol with those of other nutrients. This research involves the fields of psychobiology, pharmacology, nutrition and gastrointestinal physiology. It will advance our basic knowledge of the psychobiology of alcohol appetite and may provide practical benefits for controlling alcohol consumption in humans.

DESCRIPTION (provided by applicant): Obesity is currently a major health problem that increases the risk of many diseases, including diabetes, heart disease, hypertension and some forms of cancer. The growing prevalence of overweight and obese individuals is attributed, in part, to environmental factors such as the abundance of palatable, energy dense foods that are rich in sugar and fat. High-sugar and high-fat foods also promote overeating and obesity in laboratory animals. The orosensory properties (flavor) of high-sugar and high-fat foods are clearly attractive to animals and contribute to diet-induced overeating. Furthermore, the post-oral actions of these nutrients significantly enhance carbohydrate and fat appetites. Post-oral nutrient actions were initially considered to be exclusively inhibitory (satiating) in nature, but recent findings demonstrate that nutrients have positive (stimulating) postingestive consequences that influence food choice and consumption by conditioning flavor preference and acceptance. The onset of satiation during meals can mask the initial stimulation of intake by post-oral nutrients, which has hindered the study of these early effects. Using a new method, the proposed studies will obtain more specific access to the conditioning process that promotes ingestion in an ongoing meal and confers greater attraction to that food in subsequent meals. Animals that have been consuming a mildly palatable flavored solution paired with post-oral water are shifted to a new flavor paired with post-oral nutrient, and the changes in their ingestive responses are monitored. Increased intake in the first session of intestinal nutrient stimulation indicates that the nutrient has been detected and a signal has reached the brain. With additional methods, including the use of knockout mouse models missing elements of putative sensing and signaling mechanisms, the components of this associative process will be investigated. The overall goal of this application is to determine the processes by which orosensory and post-oral sensory stimuli become linked in the acquisition of carbohydrate and fat appetite. The specific aims of this project are to 1) Investigate carbohydrate stimulation of intake and flavor preference learning;2) Investigate fat stimulation of intake and flavor preference learning;and 3) Evaluate the role of fat taste and post-oral feedback on fat appetite and individual differences in nutrient preferences. This research involves the fields of psychology, nutrition, and gastrointestinal physiology. Understanding how flavors become linked to rewarding properties of foods, strengthening preferences and leading to overeating is crucial to finding ways to limit the intake-promoting effects of foods. This knowledge may also be applied to promote eating in clinical cases of anorexia and cachexia. PUBLIC HEALTH RELEVANCE: This project will examine the processes by which carbohydrates and fats stimulate eating and lead to preferences for foods high in these nutrients. Discovering the controls of nutrient-stimulated eating will assist the development of treatments for overeating and obesity as well as for anorexia.