This presents a particular problem for medications designed to improve mood--after all, we cannot ask a mouse if she feels more or less sad, or if she feels more like going to work than before the antidepressants. And, just like in humans, there is no blood test or brain scan that can diagnose depression.
So, how does a researcher measure depression in mice? This article in Scientific American answers that question--researchers use proxy measures. That would be behaviors that seem to indicate that the mouse is more or less depressed. For example:
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.
I'll leave it to others to decide if these proxy measures are actually measuring what they purport to measure.
Read the whole article here.