For a new study on the relationship between exercise and depression, researchers at the Karolinska Institute in Stockholm bred mice with elevated levels of an enzyme that is produced naturally through aerobic exercise, and then exposed these mice—as well as a control group—to regular, chronic stresses, like mild shocks and physical restraints, for five weeks. The mice with the higher levels of the enzyme were less likely to develop depression.

But as Gretchen Reynolds notes in The New York Times, “We can’t ask mice if they are feeling cheerful or full of woe.” So how do we determine when a mouse is feeling blue?

I called Scott Russo, the director of a Mount Sinai lab that uses rodents to study mental illness and addiction, to learn more about what researchers recognize as depression in mice and rats. “The most important thing to highlight is that none of us really feel comfortable saying that mice ‘show depression,’” he cautioned. “Depression is very complex, and I don’t know that we even have a good handle on it in humans.” Nonetheless, scientists have come up with a few signs of despondency in rodents—many of which are pretty analogous to human symptoms of depression. 

They lose their taste for sugar

“Chronically stressed mice often have a reduction in their preference for sucrose over water,” says Russo. Like most animals, mice prefer sweet tastes; when given a choice between sucrose solution and plain water, a healthy mouse will go straight for the sugary option. But if a mouse has been exposed to significant amounts of stress, it won’t discriminate. Like many depressed humans, sad mice lose their “ability to experience natural rewards”—like food—“as rewarding.”

They’re less sociable

When researchers put a mouse in an arena with an inanimate object—an empty cage, for example—and another mouse, a healthy mouse will mostly ignore the object and spend its time getting to know the other mouse. Showing a lot of interest in the inanimate object may be a sign of “social avoidance”—one of the classic symptoms of depression.

They give up faster

The “forced swim test” is the most common test of “depression” in rodents, according to David Overstreet, a researcher at the University of North Carolina’s School of Medicine. When a healthy mouse is immersed in a tank of room-temperature water, it will spend about three minutes trying to stay afloat before giving up, becoming immobile and, hopefully, being rescued by the experimenter. In a display of what Russo calls “behavioral despair,” though, a “depressed” rodent will swim for only about one minute. In another measure of “behavioral despair” called the “tail suspension test,” the rodent is hung upside-down by its tail. A healthy mouse will struggle to latch onto something and turn itself upright; a “depressed” one will give up more quickly.  

They’re less open to new experiences

When a healthy mouse is put into a large, open arena, it will explore its new environment: run around the center, find the lighted areas, climb an elevated maze. A mouse that’s been exposed to significant stress, though, will cower in the corner.

They prefer dark spaces

When placed in a maze or box with some dark and some light areas, a healthy mouse will spend more time in the light places; a “depressed” one may prefer the dark.