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

doi:10.1159/000086413

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

Bristol Neuroscience

Research output: Contribution to journal › Article (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 language	English
Pages (from-to)	129-36
Number of pages	8
Journal	Neuroendocrinology
Volume	81
Issue number	2
DOIs	https://doi.org/10.1159/000086413
Publication status	Published - 20 Jun 2005

Bibliographical note

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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title = "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",

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.",

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",

author = "Bachmann, {Cornelius G} and Alicia Bilang-Bleuel and {De Carli}, Sonja and Linthorst, {Astrid C E} and Reul, {Johannes M H M}",

year = "2005",

month = jun,

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doi = "10.1159/000086413",

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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. / Bachmann, Cornelius G; Bilang-Bleuel, Alicia; De Carli, Sonja et al.

In: Neuroendocrinology, Vol. 81, No. 2, 20.06.2005, p. 129-36.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - 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

AU - Bachmann, Cornelius G

AU - Bilang-Bleuel, Alicia

AU - De Carli, Sonja

AU - Linthorst, Astrid C E

AU - Reul, Johannes M H M

PY - 2005/6/20

Y1 - 2005/6/20

N2 - 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.

AB - 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.

KW - Administration, Oral

KW - Analysis of Variance

KW - Animals

KW - Behavior, Animal

KW - Brain/cytology

KW - Carrier Proteins/pharmacology

KW - Cell Count/methods

KW - Cyclic AMP Response Element-Binding Protein/metabolism

KW - Freezing Reaction, Cataleptic/drug effects

KW - Immunohistochemistry/methods

KW - Male

KW - Neurons/drug effects

KW - Phosphorylation/drug effects

KW - Rats

KW - Rats, Wistar

KW - Reaction Time/drug effects

KW - Steroids

KW - Stress, Psychological/metabolism

KW - Swimming

KW - Time Factors

U2 - 10.1159/000086413

DO - 10.1159/000086413

M3 - Article (Academic Journal)

C2 - 15970644

VL - 81

SP - 129

EP - 136

JO - Neuroendocrinology

JF - Neuroendocrinology

SN - 0028-3835

IS - 2

ER -

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

Abstract

Bibliographical note

Keywords

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