Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa

The overall goal of this procedure is to induce activity-based anorexia in adolescent female mice. This is accomplished by first introducing the mice to a running wheel and for at least three days continuously monitoring their running wheel activity. Next, the M are put on a restricted schedule of food access and changes in their voluntary wheel running are recorded.

Ultimately, this activity based anorexia model can show that neurobiological changes are associated with changes in an animal's behavior when given restricted access to food. It is my hope that this model of activity-based anorexia will help with improving the therapy of anorexia nervosa because it will identify discrete individual differences in the neurochemistry and neuroanatomy that underlie the resilience and vulnerability to anorexia nervosa. Though this method can provide insight into anorexia nervosa, it can also be applied to other diseases that have comorbidity with anxiety.

Generally, individual nuity, this method will struggle because each animal's vulnerability to activity based on AIA is highly variable. Thus close monitoring the animal's weight loss, eating and activity are required, or animals can per To begin setting up. Put the computer and USB hub in the animal room away from running water and foot traffic, yet within transmitter range of the running wheels.

Also use a backup power supply for the computer and USB hub using switches on the hub. Set the channel numbers to correspond to the channel numbers of all the running wheels it will monitor. Now start the running wheel manager software and confirm that the software recognizes each transmitter.

Each wheel will be listed in the program window. Under the heading wheel sensors. The software will automatically give an ID number to each wheel.

It may be helpful to note this number on the wheel. If a wheel is not recognized, replace the wheel's batteries. Next, prepare a cage for each mouse subject with bedding nestlets free access to water and a running wheel.

The running wheel must move freely without touching cage walls, food basket, or cage top. Also, confirm that the software is updating the wheel counts. To acclimate the animals house each mouse individually in a cage with a running wheel and access to about 100 grams of dry food and 50 grams of wet food in the cage.

In the software. Begin the data acquisition and storage by selecting start acquisition. From the file menu, choose the directory to which the data will be saved until stopped.

The software will record continuously every day just before the beginning of the dark phase of the light cycle. Weigh the animal, weigh wet food and weigh dry food. Refill the dry food container if it contains below 50 grams and replace the wet food container.

If the food dries out or becomes soiled with bedding, manually record the wheel count at this same time. To back up the digital data on the first day of food restriction, remove all the wet and dry food from the cage at the middle of the light cycle portion of the day. Later at the onset of the dark time, record the weight of the animal and the wheel count.

Then put about 50 grams of dry food in the hopper and provide five grams of wet food in a whe boat. Next, prepare a fresh cage with bedding and nestlets for each animal. After two hours with the food transfer, the running wheel and a few handfuls of dirty bedding to the prepared cage.

Transfer the mice to the new cages without food. At the end of the food access period, record the weight of the UNE foods and the wheel count. Repeat this process daily for the duration of the experiment.

If at any point an animal drops below 75%of its initial weight, remove it from the experiment. Other indications of excessive starvation that would indicate that the animal should be removed from the experiment include a hunched posture and inability to move around the cage. The animal may be cold to the touch and fail to eat during the two hours of food access.

After three days of food restriction, end the experiment. Either euthanize the animal to harvest tissues or allow the animals to recover. For further behavioral testing in the software, click the end acquisition option under the file menu.

The data are now saved in a WLS file in the directory chosen At the start of the experiment, remove the running wheels from the cages and then remove their batteries. Recovering animals should be allowed ad libido, access to food. Now, export the data to a spreadsheet.

Choose the export option in the file menu and select the desired WLS files in the source data file option. Next, select the start and end date and time, and finally select each wheel sensor for export. In the wheel sensors list, the data can then be analyzed as needed to study the effect of a b.

In a similar population to human anorexia nervosa, female adolescent mice were acclimated to the wheel at P 36. Soon after the onset of puberty, food deprivation was started on P 40 and their body weight sharply decreased control animals did not have running wheels or food restrictions. The starved animals ran excessively after the onset of food restriction.

Detailed analysis of wheel activity showed a circadian pattern. Curiously, even during food access, starving animals chose to use the running wheel. After food restriction began, some animals showed an increase in activity just prior to the time of feeding, which may be called food Anticipatory activity One masters to setting up a cohort to undergo activity based scenario can be achieved in a couple of hours if it is performed properly.

While attempting this procedure, it's important to remember to record the wheel counts manually at least once per day. Unexpected disruption of the power line or depletion of the batteries can disrupt the computer generated wheel counting Following this procedure. Other methods such as immuno cyto chemistry, electrophysiology, and behavioral testing can be performed in order to answer additional questions such as how activity-based anorexia induction affects brain anatomy, biophysical properties, and behavior.