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

Shannon L. Gourley1, Jane R. Taylor2

1 Department of Psychiatry, Yale University, New Haven, Connecticut, 2 Department of Psychology, Yale University, New Haven, Connecticut
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.32
DOI:  10.1002/0471142301.ns0932s49
Online Posting Date:  October, 2009
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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.

Keywords: corticosterone; stress; striatum; CREB; antidepressant; anhedonia

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Table of Contents

  • Introduction
  • Basic Protocol 1: Oral Corticosterone Exposure in Rats and Mice
  • Commentary
  • Literature Cited
  • Figures
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Basic Protocol 1: Oral Corticosterone Exposure in Rats and Mice

  • Corticosterone hemisuccinate (4‐pregnen‐11β 21‐DIOL‐3 20‐DIONE 21‐hemisuccinate; Steraloids)
  • Tap water
  • 10 N NaOH and HCl for adjusting pH of solutions
  • C57bl/6 male mice (group housed: 4 to 5/cage) or Sprague‐Dawley male rats (pair housed), at least 12 weeks of age (e.g., Charles River Laboratories, Jackson Labs)
  • Standard laboratory housing, diet, and light cycle regulation
  • Metric balance
  • 1‐ or 2‐liter clean glass bottles with lids for solution storage
  • Disposable Pasteur pipets (e.g., Fisher Scientific)
  • pH meter
  • Stir plate, magnetic stir bar
  • Standard laboratory rodent water bottles
NOTE: CORT solutions must be changed within 72 hr of dissolution, as CORT will begin to degrade once in solution. Dissolved CORT should be stored at 4°C; stirring at 4°C will also slow degradation. In solid form, CORT hemisuccinate is stable and can be used until the manufacturer's expiration date. Solid CORT can be stored at room temperature or at 4°C.
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Literature Cited

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