The selective glucocorticoid receptor antagonist ORG 34116 decreases immobility time in the forced swim test and affects cAMP-responsive element-binding protein phosphorylation in rat brain

Cornelius G Bachmann, Alicia Bilang-Bleuel, Sonja De Carli, Astrid C E Linthorst, Johannes M H M Reul

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Glucocorticoid receptor (GR) antagonists can block the retention of the immobility response in the forced swimming test. Recently, we showed that forced swimming evokes a distinct spatiotemporal pattern of cAMP-responsive element-binding protein (CREB) phosphorylation in the dentate gyrus (DG) and neocortex. In the present study, we found that chronic treatment of rats with the selective GR antagonist ORG 34116 decreased the immobility time in the forced swim test, increased baseline levels of phosphorylated CREB (P-CREB) in the DG and neocortex and affected the forced swimming-induced changes in P-CREB levels in a time- and site-specific manner. Overall, we observed that, in control rats, forced swimming evoked increases in P-CREB levels in the DG and neocortex, whereas in ORG 34116-treated animals a major dephosphorylation of P-CREB was observed. These observations underscore an important role of GRs in the control of the phosphorylation state of CREB which seems to be of significance for the immobility response in the forced swim test and extend the molecular mechanism of action of GRs in the brain.

Original languageEnglish
Pages (from-to)129-36
Number of pages8
JournalNeuroendocrinology
Volume81
Issue number2
DOIs
Publication statusPublished - 20 Jun 2005

Bibliographical note

Copyright 2005 S. Karger AG, Basel

Keywords

  • Administration, Oral
  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Brain/cytology
  • Carrier Proteins/pharmacology
  • Cell Count/methods
  • Cyclic AMP Response Element-Binding Protein/metabolism
  • Freezing Reaction, Cataleptic/drug effects
  • Immunohistochemistry/methods
  • Male
  • Neurons/drug effects
  • Phosphorylation/drug effects
  • Rats
  • Rats, Wistar
  • Reaction Time/drug effects
  • Steroids
  • Stress, Psychological/metabolism
  • Swimming
  • Time Factors

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