Models of Depression: Unpredictable Chronic Mild Stress in Mice

Major depression is a complex psychiatric disorder characterized by affective, cognitive, and physiological impairments that lead to maladaptive behavior. The high lifetime prevalence of this disabling condition, coupled with limitations in existing medications, make necessary the development of improved therapeutics. This requires animal models that allow investigation of key biological correlates of the disorder. Described in this unit is the unpredictable chronic mild stress mouse model that is used to screen for antidepressant drug candidates. Originally designed for rats, this model has been adapted for mice to capitalize on the advantages of this species as an experimental model, including inter-strain variability, which permits an exploration of the contribution of genetic background, the ability to create transgenic animals, and lower cost. Thus, by combining genetic features and socio-environmental chronic stressful events, the unpredictable, chronic mild stress model in mice can be used to study the etiological and developmental components of major depression, and to identify novel treatments for this condition.