How Depression and Anxiety are Studied in Animals
When you're attempting to study a human condition in animals, you first must develop a model of that condition. We may not be able to tell when a mouse has schizophrenia or depression, but we can model these disorders in order to study them. This can be done in various ways, but these models must be deemed as valid analogues for their human counterpart. Does this model produce similar symptoms? Do they respond to treatments that work in humans? Does it have the same cause as the disorder? These are some questions used to determine the validity of a model.
In this post we will discuss a few different experiments that are frequently used when studying depression and anxiety. Though first, we have to look at how models for these conditions are established in animals (we will go over specifically mice). The most common model for depression in mice is chronic mild stress (CMS), which increases both depression-like and anxiety driven behaviors. It is established by exposing the animal to random, unpredictable, unpleasant events (drastic temperature change, food or water deprivation, loud noises, etc.) over a period of 2+ weeks. Others may involve genetically knocking out entire genes, separation from the mother at a young age, and more. Recently, it was found that a model of depression can be established by administering broad-spectrum antibiotics for 3 weeks, mimicking antibiotic induced depression that is sometimes seen in humans. The model used and how it is established are important factors and can have effects on the results of a study.
Let’s take a look at some commonly used behavioral tests.
Depression
Tail Suspension Test
In this test the animal is hung from the ceiling by its tail. During, the animal will flail and attempt to escape, eventually giving up. The time until the animal becomes immobile is what is measured here. The shorter the time the animal tries to escape, the more “depression-like” their behavior is. You could expect an antidepressant to increase struggle time in a depression model mouse.
Forced Swim Test
Here, animals are placed in a container filled with water. At first they try to escape, until they give up and do only what's necessary to keep their nose above water. Similar to the tail suspension, this test measures time until immobility and the shorter that time the more “depression-like” the behavior. Again, an antidepressant should increase time spent struggling.
Sucrose Preference Test
This is a little different as it tests for anhedonia, decreased ability to experience pleasure, a symptom of depression. In the animal’s cage they are given two tubes they can access water from. One contains normal water, the other contains a water and sucrose solution, essentially sugar water. The measured behavior here is the percent of the volume of sucrose water consumed over the total volume of liquid consumed. Since rodents have an inherent interest in sugar you’d expect them to prefer the sucrose water at a high rate, but in depression models you see a significant decrease in sucrose preference. Here an antidepressant should increase sucrose intake.
Anxiety
Elevated Plus Maze
This test is not so much a maze, as it is a test for animal anxiety. It consists of a “+” shaped platform raised off the floor a few feet. 2 of the arms are closed in, providing the animal with shelter. This test is based on mice’s natural aversion to both elevated and open areas. The animal is placed in one of the closed arms, and the measured behaviors are how many times they enter the open, and the total time they spend there. More enters and longer times in the open are associated with less anxiety, so you’d expect anxiolytic drugs to increase their time spent on the open arms.
Open Field Test
Here mice are simply placed in a square box and observed. Since they naturally exhibit a behavior known as thigmotaxis, they like touching walls as they move around. A less anxious mouse will spend more time exploring the center, while a more anxious mouse will stick to the walls. An anxiolytic drug would likely cause the mouse to spend less time hugging the walls, and spend more time in the center of the field.
If you want to see video examples of these, visit jove.com and search the test name.
What typically happens in a study is you have a control group, normal mice, and an experimental group, the ones modeling a condition. Both groups will be run through the desired tests and you can compare the results. Then you administer a drug of choice (antidepressant, anti-anxiety medication, etc.) to the experimental group and see if their results become closer to the control group, exhibiting less depression-like or anxiety behaviors. If so, the drug shows promise for being effective in humans.
There is certainly more that goes into a complete study, but this should draw the big picture and give some insight into how experiments are run in animals.