Use of a time-restricted access to food diet to achieve and maintain weight reduction in mice.

Abstract

Recent years have seen the development of mouse models of a wide range of psychological disorders and afflictions to the central nervous system, including Alzheimer's disease, anorexia nervosa, abnormal anxiety, attention deficit hyperactivity disorder, autism, major depression, Fragile X Syndrome, Huntington's disease, obsessive-compulsive disorder, Parkinson's disease, schizophrenia, and Tourette's syndrome. Mouse models are used chiefly to study neurophysiological processes, but behavior is sometimes studied as well. One reason to study the behavior is to help establish the validity of the model: Do the mice manifest the expected behavioral abnormalities? Furthermore, the study of behavior may provide new insights into underlying neurophysiological processes. Behavior also affords a means to measure the efficacy of treatments designed to prevent, mitigate or reverse neurophysiological abnormalities. Behavior analysts have taken an increasing interest in mice as research subjects to judge from recent publications in The Journal of the Experimental Analysis of Behavior (e.g., Belke & Garland, 2007; Leslie, Shaw, Gregg, McCormick, Reynolds, & Dawson, 2005; McKerchar, Zarcone, & Fowler, 2005; Papachristos & Gallistel, 2006; Zarcone, Chen, & Fowler, 2007). However, behavior analytic animal research traditionally has been conducted with pigeons and rats, and unfamiliarity with mice may deter some from pursuing research with mouse models. To help remedy this concern, we examined whether time-restricted feeding procedures would provide a simple means of allowing researchers to achieve and maintain an appropriate level of food deprivation in mice. There are two basic strategies used to establish food deprivation in operant research. One strategy is to restrict the amount of food subjects are allowed to consume and the other is to restrict the length of time subjects are allowed to eat (as shorthand, these are referred to below as and diets, respectively). Under the former approach, subjects are weighed daily and the size of the food ration is adjusted to maintain weights at a given level (and by extension, ensure a constant level of food deprivation). Hurwitz and Davis (1983) observed that this procedure quickly predominated behavior-analytic animal research, although it is not without disadvantage. The restricted-amount procedure requires that subjects be housed individually to ensure that all subjects receive the appropriate of food. This, in turn, limits research on social processes. The restricted-amount procedure is also impractical to implement because the weight of both the subject and the food ration must be carefully monitored. The difficulty of calculating an appropriate amount of food is compounded if the amount of food subjects earn during data collection is inconstant or if data collection is not performed daily. In view of the shortcomings of the restricted-amount procedure, Hurwitz and Davis recommended that researchers use instead the restricted-time procedure. Hurwitz and Davis demonstrated the relative advantages of this approach using six, male, Long-Evans rats. Subjects had food access for 1 or 2 hours each day (1 hr when the food was placed inside the subjects' cages, 2 hrs when the food was available through an external wire-mesh hopper). They found that when the procedure was introduced, subjects lost approximately 20% of their free-feeding weights, achieving in a few days the 80% level of weight reduction used in many animal studies. Continued use of the procedure, however, did not result in further weight loss, and by the end of 20 days of observations, mean weights had stabilized to 78.5% of free-feeding levels. Hurwtiz and Davis found that the procedure was effective even when subjects could obtain additional food during experimental sessions with a variable-interval schedule of reinforcement. …