Chronic social defeat stress and social interaction test. Resident aggressor mice (e.g., white CD-1) are singly housed in cages for several days prior to testing to establish territory. The experimental intruder mouse (e.g., C57BL/6) is placed into the home cage of the aggressor and the two mice interact for 5–10 min (physical stress, left). Typically, the experimental mouse is quickly attacked by the aggressor mouse, and these attacks continue throughout the duration of the physical stress period. The experimental mouse is then moved to the other side of a perforated divider where it is safe from further attack, but can still see, hear, and smell the aggressor (sensory stress, middle). The experimental mouse is housed here for 24 h. The cycle then repeats for 10 or more days with the experimental mouse exposed to a novel aggressor mouse each day. Social interaction (SI) testing (right) is used following the chronic stress to evaluate social withdrawal as a measure of stress susceptibility. Susceptible mice exhibit social withdrawal and spend less time in the interaction zone (red) with the social target, and more time in the corners (yellow), withdrawn and isolated.