Acute stress-induced sensitization of the pituitary-adrenal response to heterotypic stressors: Independence of glucocorticoid release and activation of CRH1 receptors

Xavier Belda, Núria Daviu, Roser Nadal, Antonio Armario

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

A single exposure to some severe stressors causes sensitization of the hypothalamic-pituitary-adrenal (HPA) response to novel stressors. However, the putative factors involved in stress-induced sensitization are not known. In the present work we studied in adult male rats the possible role of glucocorticoids and CRH type 1 receptor (CRH-R1), using an inhibitor of glucocorticoid synthesis (metyrapone, MET), the glucocorticoid receptor (GR) antagonist RU38486 (mifepristone) and the non-peptide CRH-R1 antagonist R121919. In a first experiment we demonstrated with different doses of MET (40-150. mg/kg) that the highest dose acted as a pharmacological stressor greatly increasing ACTH release and altering the normal circadian pattern of HPA hormones, but no dose affected ACTH responsiveness to a novel environment as assessed 3 days after drug administration. In a second experiment, we found that MET, at a dose (75. mg/kg) that blocked the corticosterone response to immobilization (IMO), did not alter IMO-induced ACTH sensitization. Finally, neither the GR nor the CRH-R1 antagonists blocked IMO-induced ACTH sensitization on the day after IMO. Thus, a high dose of MET, in contrast to IMO, was unable to sensitize the HPA response to a novel environment despite the huge activation of the HPA axis caused by the drug. Neither a moderate dose of MET that markedly reduced corticosterone response to IMO, nor the blockade of GR or CRH-R1 receptors was able to alter stress-induced HPA sensitization. Therefore, stress-induced sensitization is not the mere consequence of a marked HPA activation and does not involve activation of glucocorticoid or CRH-R1 receptors. © 2012 Elsevier Inc.
Original languageEnglish
Pages (from-to)515-524
JournalHormones and Behavior
Volume62
DOIs
Publication statusPublished - 1 Sep 2012

Keywords

  • ACTH
  • CRH
  • Corticosterone
  • Glucocorticoids
  • Immobilization stress
  • Metyrapone
  • Mifepristone
  • Pituitary-adrenal axis
  • R121919
  • Sensitization

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