In “Lifting the Black Cloud,” Robin Henig surveys the search for new, improved antidepressants. Much research in the area involves laboratory mice and rats. Here, Henig explains how scientists determine whether a rodent is depressed.

It’s hard to develop an animal model for depression. As Michael Kaplitt  of Cornell Medical College puts it, “A mouse can’t tell you how it’s feeling.” Scientists have had to come up with proxy behaviors, actions that they interpret as “depressionlike,” to measure whether particular drugs or therapies are having an effect. To identify depression in laboratory animals, investigators rely on the following:

Forced swimming test. The rat or mouse is placed into a cylinder partially filled with water from which escape is difficult. The longer it swims, the more actively it is trying to escape; if it stops swimming, this cessation is interpreted as depressionlike behavior, a kind of animal fatalism.

Tail suspension test. A mouse (it does not work in rats) is hung upside down from its tail, and the sooner it stops wiggling, the greater its depressionlike behavior is said to be. Administering an antidepressant usually increases the length of time that a mouse will struggle when suspended by the tail.

Sugar water preference. The preference an animal shows for sugar water is taken as an indication of its ability to derive pleasure, a quality that is missing in depression. Most rodents, when given two identical-looking sources of water, will drink much more of the sweetened water than the plain water. Rodents exposed to chronic stress or whose brains have been manipulated show no such preference.