Early post-stress administration of MR or GR antagonist in adolescent female rats restored anxiogenic-like behavior and modified the HPA axis response in the adulthood

Brain Res. 2022 May 1;1782:147833. doi: 10.1016/j.brainres.2022.147833. Epub 2022 Feb 18.


Several brain structures responsible for controlling stress responses reach maturity during adolescence. Therefore, acute or chronic stress in prepuberty may negatively affect stress responses as well as behavior in adulthood. The hypothalamus-pituitary-adrenal axis (HPA) is part of the stress system whose inhibitory control is regulated by glucocorticoids through mineralocorticoid (MR) and glucocorticoid (GR) receptors. In this study, we aimed to determine whether MR or GR blockade after stress in adolescence prevents changes in exploratory behavior and HPA axis control in adult female rats. Adolescent female rats (26 days old) were submitted to one or seven daily restraint sessions followed by administration of MR (spironolactone) or GR (RU-486) antagonists. At 60 days old, animals were evaluated in the elevated plus maze and at 61 days old rats were subjected to acute stress to evaluate the HPA response. The chronic restraint in the adolescence induced an anxiogenic effect in the adult animals that was reverted by either MR or GR antagonist. In the same way chronic stress reduced the HPA axis activity by blunted corticosterone (CORT) secretion and decreased the activation of Corticotropin Releasing Hormone (CRH) neurons in the paraventricular nucleus. The post-stress blocking of GR independently restored the CORT secretion without effect on central activation. The acute stress in the adolescence had minor enduring effects. We concluded that the use of RU-486 and spironolactone after stress in the early adolescence can improve behavioral changes induced by stress whereas RU-486 only showed effect on the HPA axis response in adulthood.

Keywords: Adolescence; CRH; Corticosterone; RU-486; Spironolactone; Stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety*
  • Corticosterone / pharmacology
  • Corticotropin-Releasing Hormone / metabolism
  • Female
  • Glucocorticoids / pharmacology
  • Hypothalamo-Hypophyseal System*
  • Mifepristone / pharmacology
  • Mineralocorticoid Receptor Antagonists* / pharmacology
  • Pituitary-Adrenal System*
  • Rats
  • Receptors, Glucocorticoid* / antagonists & inhibitors
  • Spironolactone / pharmacology
  • Stress, Psychological


  • Glucocorticoids
  • Mineralocorticoid Receptor Antagonists
  • Receptors, Glucocorticoid
  • Spironolactone
  • Mifepristone
  • Corticotropin-Releasing Hormone
  • Corticosterone