Pre-pubertal stress exposure affects adult behavioral response in association with changes in circulating corticosterone and brain-derived neurotrophic factor

Noam Bazak, Nitsan Kozlovsky, Zeev Kaplan, Michael Matar, Hava Golan, Joseph Zohar, Gal Richter-Levin, Hagit Cohen

Research output: Contribution to journalArticlepeer-review


Early-life stress produces a cascade of neurobiological events that cause enduring changes in neural plasticity and synaptic efficacy that appear to play pivotal roles in the pathophysiology of post-traumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF) has been implicated in the neurobiological mechanisms of these changes, in interaction with components of the stress response, such as corticosterone. This study examined the consequences of juvenile stress for behavior during adulthood in association with circulating corticosterone levels and BDNF expression. The experiments examined single exposure to predator scent stress (soiled cat litter for 10 min) as compared to repeated exposure, early in life and later on. Behavioral responses were assessed in the elevated plus maze and the acoustic startle response paradigms at 28, 60 and 90 days of age. Plasma corticosterone was measured and brain areas analyzed for BDNF levels. The results show that juvenile stress exposure increased anxiety-like behavior and startle amplitude and decreased plasma corticosterone. This response was seen immediately after exposure and also long term. Adult stress exposure increased anxiety-like behavior, startle amplitude and plasma corticosterone. Exposure to both early and later life trauma elicited reduced levels of corticosterone following the initial exposure, which were not raised by re-exposure, and elicited significant downregulation of BDNF mRNA and protein levels in the hippocampus CA1 subregion. The consequences of adult stress exposure were more severe in rats were exposed to the same stressor as juveniles, indicated increased vulnerability. The results suggest that juvenile stress has resounding effects in adulthood reflected in behavioral responses. The concomitant changes in BDNF and corticosterone levels may mediate the changes in neural plasticity and synaptic functioning underlying clinical manifestations of PTSD.

Original languageEnglish
Pages (from-to)844-858
Number of pages15
Issue number6
StatePublished - Jul 2009

Bibliographical note

Funding Information:
Funding for this study was provided by the NARSAD Grant to H.C.; the NARSAD had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.


  • Anxiety-like behavior
  • Brain-derived neurotrophic factor (BDNF)
  • Corticosterone
  • Early-life stress
  • Post-traumatic stress disorder

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry


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