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Anorexia nervosa (AN) is an eating disorder that is thought to emerge through biological predisposition(s) within sociocultural context(s). Practical and ethical concerns limit study of the etiology of this disorder in humans, and in particular the biological aspects. Laboratory animal models have a pivotal role in advancing our understanding of the neurobiological, physiological and behavioral aspects of this disorder, and developing new treatment strategies. One shortcoming of animal models, including activity based anorexia (ABA) in rodents, is that they cannot fully capture the contextual aspects of AN. In this article we discuss the merits of an alternate approach, cost-based anorexia (CBA). CBA is conceptually founded in behavioral economics and its magnitude is influenced by several relevant contextual aspects of feeding., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Intake and body weight were recorded in a closed economy as male and female C57BL/6 mice progressed through either fixed interval (FI) or fixed unit price (FUP) schedules of cost for 20-mg food pellets. Access to food was constrained to four 40 min food opportunities (FOs) per day, spaced 4-h apart through the dark phase. Nose poke responses and pellet deliveries were collected at 10-s resolution to allow pellet-by-pellet analysis. In the FI protocol, mice maintained adequate food intake and body weight through the study, even though at the highest FI (50-s) they spent the entire 40-min FOs engaged in eating at or near the maximum rate allowed by the schedule. In the FUP protocol, mice greatly reduced their intake and lost weight at the highest FUP (50 responses/pellet). The analysis of response and pellet distributions showed these mice were not filling the FOs with responding and ate less at dusk (FO #1) and dawn (FO #4) than at FOs #2 and 3 in the middle of the night. The principal, and unexpected, sex difference was that females tended to eat more than males despite lower body weight, but behavioral changes as a function of feeding cost or schedule were qualitatively similar in both sexes. These results show that slow eating as imposed by an FI is not sufficient to produce hypophagia and, in the FUP protocol, hypophagia cannot be explained by slowed eating due to response requirements. We discuss the role of effort or time in FUP-induced anorexia, and suggest this murine model may emulate some aspects of human anorexia nervosa better than current activity-based protocols., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Ad libitum feeding patterns in mice show substantial differences between laboratories, in addition to large individual and time-of-day differences. In the present study, we examine how mice work for food when access to food is temporally restricted and so they are forced to take discrete meals. In a first experiment, separate groups of ICR:CD1 mice were given access to food for 4, 8 or 16 opportunities or meals per day, with the duration of access at each opportunity adjusted reciprocally so that the total time of availability was 160 min per day in all three conditions. During the periods of availability, mice were able to earn food pellets by nose poke responses, according to an incrementing series of fixed unit prices (FUP: 2, 5, 10, 25) with each schedule in force for 3-4 days. Total food intake was similar in all three groups, indicating that mice generally were able to adjust their intake to a range of temporal availabilities. In each group, food demand fell as FUP increased. In the 8 and 16 meal groups, no food was eaten in many of the opportunities. Within an opportunity, the rate of intake generally declined with time, indicative of satiation. At low FUPs, later opportunities in each day were associated with smaller meals than earlier opportunities; in contrast, at high FUPs the first opportunity was also a small meal. Collectively, these results show that mice eat less at higher costs but not because of time constraints of the schedule: instead, they exhibit an elective anorexia. In the second experiment, we examined whether snacking between imposed meals would affect subsequent meal(s). Mice were adapted to the foregoing 8 opportunity protocol. Then, half the mice received free snacks of sugar cubes after the 3rd, 4th and 5th meal opportunities and the intakes of sugar and pellets were examined at low and high unit costs for pellets (FUP2 and 25). At FUP2, mice decreased demand for pellets and compensated energetically for the sugar they consumed. At FUP25, mice also decreased demand, but by less than the energy obtained from sugar. These data show that choice for pellets over a free palatable snack, and subsequent compensation of energy intake, is modified by effort and demand., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Male mice (Mus musculus) of a mixed B6/129 background were used to establish food demand functions in a closed economy. The mice lived continuously in operant chambers and worked for 20-mg nutritionally complete food pellets. First, a series of incrementing fixed ratio (FR) costs per pellet were imposed, and the results showed that demand declined as unit price increased. The number of meals taken per day was dependent on the temporal criterion used to define a meal, but the number of meals did not change across the FR series. Next, a series of incrementing progressive ratio (PR) schedules were used, and a meal was defined by a programmed schedule reset interval. Total food intake declined slightly, and the mean meal size also decreased, across the series. Lastly, a nose poke response requirement was imposed as the procurement cost to activate a lever press device for food; under these conditions the meal number changed dramatically as the procurement cost was increased, whereas total intake declined only modestly. These data show in mice that large changes in unit price or consummatory cost have relatively small effects on demand and meal patterns, but small amounts of foraging (procurement) cost have very large effects.

Recent findings in this laboratory with regard to tolerance to fenfluramine anorexia are reviewed with respect to generality of the behavioural phenomenon. A systematic relationship between initial body weight and fenfluramine-induced weight change in rats is described. The possible roles of peripheral factors in fenfluramine anorexia and tolerances, including gastric emptying and peripheral serotonin, are discussed. The role of central factors is also considered. It appears that fenfluramine, and possibly other anorectic agents have multiple sites of action and affect multiple behaviours. Some clinical implications are noted.

Administration of D-fenfluramine immediately following ingestion of a distinctively flavored solid or liquid diet led to subsequent rejection of that flavor when offered in a two-flavor choice test. This effect occurred with both solid and liquid diets.

The characteristics of the appetite for NaCl in humans differ in some aspects from those in other species. The mechanisms of appetite for NaCl have been studied in detail in two species, rats and sheep. We review the treatments known to induce an appetite for NaCl in rats, with special reference to differences among strains in their spontaneous preference for NaCl solution. The current view of the mechanism is critically appraised, with particular emphasis on the role of angiotensin II, mineralocorticoids, cerebroventricular sodium transport, and the relation between preference for NaCl and the concentration of sodium in saliva. The appetite for NaCl in rodents other than rats is considered next, and reveals that mice, hamsters and gerbils are reluctant to ingest NaCl either spontaneously or after treatment with several of the natriorexigenic stimuli that are effective in rats. The characteristics of the appetite for NaCl in non-rodent species, including sheep, rabbit, dog, and non-human primates, are then described. We discuss some of the possible differences in mechanism that might account for this behavioral diversity among species.