Recent evidence suggests substantial overlap between mood and anxiety disorders, both in clinical presentation and associated features. A theoretical framework to account for this overlap focuses on negative affectivity, defined as the disposition to experience negative emotional states, including fear, sadness, and guilt. This model has been successful in explaining the co-occurrence of depressive and anxiety disorders in humans. As a next step, development of an animal model focused on both depression- and anxiety-relevant behaviors may advance understanding of depression-anxiety symptom overlap, relations of these disorders with associated medical conditions and responses to treatment. This study was designed to investigate inducible and quantifiable depressionand anxiety-like behaviors in prairie voles (Microtus ochrogaster). Adult, female prairie voles were exposed to 4 weeks of social pairing (control) or isolation, an established stressor for socially monogamous mammals (including humans). Operational measures of depression (sucrose intake and behaviors in the forced swim test), anxiety (behaviors in the elevated plus maze), and aggression (responses to an unrelated prairie vole pup) were investigated. Social isolation induced a progressive decline in sucrose intake and increased immobility time during the forced swim test. Social isolation also decreased the amount of time spent in the open arms of the elevated plus maze, and increased pup-directed attack behavior. The current findings suggest that isolation induces behaviors reflecting elevated negative affect. These results may provide a foundation for creating a rodent model to examine the mechanisms underlying comorbid mood and anxiety disorders.