Recapitulation and Reversal of a Persistent Depression‐like Syndrome in Rodents

Alterations in multiple biological functions, such as transcription factor activity, are implicated in the neurobiology of depression, based primarily on the characterization of antidepressant efficacy in naïve rodents rather than on models that capture the protracted feelings of anhedonia and helplessness that typify depression. This unit presents rat and mouse models of depression that involve chronic oral exposure to the stress‐associated adrenal hormone, corticosterone (CORT), resulting in anhedonic‐ and helplessness‐like behaviors that are persistent yet reversible by chronic antidepressant treatment. Prior CORT exposure also chronically influences molecular targets hypothesized to contribute to negative mood. One example is phosphorylation of cAMP response element binding protein in the hippocampus and nucleus accumbens. Prior chronic CORT exposure provides an alternative method to chronic mild stress models of depression that is easily replicable and persists well beyond the CORT exposure period, thereby modeling the persistent depressive‐like state in humans. Curr. Protoc. Neurosci . 49:9.32.1‐9.32.11. © 2009 by John Wiley & Sons, Inc.