Assessing Activity-based Anorexia in Mice

Summary

Mice individually housed with a running wheel while given limited access to food develop reductions in food consumption and increase activity on the running wheel. This experimental phenomenon is called activity-based anorexia. This paradigm provides an experimental tool for studying the neurobiology and behaviors underlying aspects of anorexia nervosa.

Abstract

Rodents develop activity-based anorexia (ABA) when exposed to a restricted feeding schedule and allowed free access to a running wheel. These conditions lead to a life-threatening reduction in body weight. However, rodents exposed to only one of these conditions ultimately adapt to re-establish normal body weight. Although increased running coupled with reduction in voluntary food intake appear paradoxical under ABA conditions, ABA behavior is observed across numerous mammalian species.

The ABA paradigm provides an animal model for anorexia nervosa (AN), an eating disorder with severe dysregulation of appetite-behavior. Subjects are singly housed with free access to a running wheel. Each day, the subject is offered food for a limited amount of time. During the course of the experiment, a subject's body weight decreases from high activity and low caloric intake. The duration of the study varies based on how long food is offered daily, the type of food offered, the strain of mouse, if drugs are being tested, and environmental factors.

A lack of effective pharmacological treatments for AN patients, their low quality of life, high cost of treatment, and their high mortality rate indicate the urgency to further research AN. We provide a basic outline for performing ABA experiments with mice, offering a method to investigate AN-like behavior in order to develop novel therapies. This protocol is optimized for use in Balb/cJ mice, but can easily be manipulated for other strains, providing great flexibility in working with different questions, especially related to genetic factors of ABA.

Introduction

Since 1953, rodents have been reported to show a paradoxical hyperactivity on running wheels when they are given free access to the wheels while undergoing voluntary hypophagia when food availability is restricted¹. Conversely, rodents do not rapidly drop in body weight when offered food on a schedule without running wheels or when housed with running wheels and offered food ad libitum^1,2,3. The ABA model reliably results in dramatic declines in body weight, hypophagia, hypothermia, loss of estrus, and increased stimulation of the HPA....

Protocol

All methods described here have been approved by the Institutional Animal Care and Use Committee (IACUC) of the University of California, San Diego.

1. Mice

1. Choose the appropriate mouse strain for the study.
2. Purchase mice from a supplier or amplify a line to obtain appropriate experimental numbers.
3. Group-house purchased mice in the animal facility for at least 1 week prior to beginning the study to allow for an ample acclimation period.
4. Begin the pre-experimental acclimation phase when mice are 8 weeks old.

2. Housing

1. Choose cages that are large enough ....

Results

Brain-derived neurotrophic factor (BDNF), a protein that contributes to the regulation of feeding as well as weight maintenance, is reduced in the serum of patients with AN³⁵. This experiment assessed the effects of scheduled feeding, running wheel access, or both on BDNF expression within the hippocampus (HPC), ventral tegmental area (VTA), nucleus accumbens (NAc), and medial prefrontal cortex (mPFC). Expression of neuronal cell adhesion molecule 1 (NCAM1) was als.......

Discussion

The ABA experiment can be modified by experimenters to test different strains, ages, drugs, and various other variables of AN. Bearing in mind genetic variability, adjustments to the running wheel or food access period would increase or decrease the severity of symptoms and rate of dropout. This can serve to increase or decrease the length of the experiment, depending on the experimental question of interest.

Accurate measurement of food intake is a critical part of the ABA paradigm, but can .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Wireless Low Profile Running Wheels, Hubs, Software	Med Associates	ENV-047
Standard Teklad Rodent Chow	Envigo	8604
8 Week Old Mice	Jackson Laboratories	Balb/cJ	Strain used in our study - Can use other strains to assess ABA
Scout Pro Scale 200 g	Ohaus	SPE202	Used to weigh mice
Scout Pro Scale 400 g	Ohaus	SPE402	Used to weight food