Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress

J. Marit Arp, Judith P. ter Horst, Manila Loi, Jan den Blaauwen, Eline Bangert, Guillen Fernandez, Marian Joels, Melly S. Oitzl, Harm J. Krugers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

48 Citations (Scopus)

Abstract

Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated (i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal day 2 to 9- affects conditioned fear in adult mice and (ii) whether these effects can be prevented by blocking glucocorticoid receptors (GRs) at adolescent age. In adult male and female mice, ELS did not affect freezing behavior to the first tone 24 h after training in an auditory fear-conditioning paradigm. Exposure to repeated tones 24 h after training also resulted in comparable freezing behavior in ELS and control mice, both in males and females. However, male (but not female) ELS compared to control mice showed significantly more freezing behavior between the tone-exposures, i.e. during the cue-off periods. Intraperitoneal administration of the GR antagonist RU38486 during adolescence (on postnatal days 28-30) fully prevented enhanced freezing behavior during the cue-off period in adult ELS males. Western blot analysis revealed no effects of ELS on hippocampal expression of glucocorticoid receptors, neither at postnatal day 28 nor at adult age, when mice were behaviorally tested. We conclude that ELS enhances freezing behavior in adult mice in a potentially safe context after cue-exposure, which can be normalized by brief blockade of glucocorticoid receptors during the critical developmental window of adolescence. (C) 2016 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)30-38
Number of pages9
JournalNeurobiology of Learning and Memory
Volume133
DOIs
Publication statusPublished - Sep-2016
Externally publishedYes

Keywords

  • Early life stress
  • Fear conditioning
  • Fear
  • Memory
  • Glucocorticoid receptor
  • Anxiety
  • ANTAGONIST MIFEPRISTONE NORMALIZES
  • MATERNAL-CARE
  • HIPPOCAMPAL NEUROGENESIS
  • SYNAPTIC PLASTICITY
  • ANXIETY DISORDERS
  • CHILDHOOD TRAUMA
  • MENTAL-DISORDERS
  • JUVENILE STRESS
  • SEX-DIFFERENCES
  • BRAIN

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