Genetic stress-reactivity, sex, and conditioning intensity affect stress-enhanced fear learning

K. J. Przybyl, S. T. Jenz, P. H. Lim, M. T. Ji, S. L. Wert, W. Luo, S. A. Gacek, A. K. Schaack, E. E. Redei*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


The Stress-Enhanced Fear Learning (SEFL) model of posttraumatic stress disorder (PTSD) reveals increased fear memory in animals exposed to stress prior to contextual fear conditioning (CFC), similar to the increased likelihood of developing PTSD in humans after prior stress. The present study utilized the SEFL model by exposing animals to restraint stress as the first stressor, followed by CFC using foot-shocks with 0.6 mA or 0.8 mA intensity. Adult males and females from the two nearly isogenic rat strains, the genetically more stress-reactive Wistar Kyoto (WKY) More Immobile (WMI), and the less stress-reactive WKY Less Immobile (WLI) were employed. Percent time spent freezing at acquisition and at recall differed between these strains in both prior stress and no stress conditions. The significant correlations between percent freezing at acquisition and at recall suggest that fear memory differences represent a true phenotype related to the stress-reactivity differences between the strains. This assumption is further substantiated by the lack of effect of either conditioning intensity on percent freezing in WLI males, while WMI males were affected by both intensities albeit with opposite directional changes after prior stress. Differences between the sexes in sensitivity to the two conditioning intensities became apparent by the opposite directional and inverse relationship between fear memory and the intensity of conditioning in WMI males and females. The present data also illustrate that although corticosterone (CORT) responses to prior stress are known to be necessary for SEFL, plasma CORT and percent freezing were positively correlated only in the stress less-reactive WLI strain. These differences in baseline fear acquisition, fear memory, and the percent freezing responses to the SEFL paradigm in the two genetically close inbred WMI and WLI strains provide a unique opportunity to study the genetic contribution to the variation in these phenotypes.

Original languageEnglish (US)
Article number107523
JournalNeurobiology of Learning and Memory
StatePublished - Nov 2021


  • Contextual fear conditioning
  • Corticosterone
  • Foot-shock intensity
  • Nr3c1 expression
  • Testosterone
  • WLI
  • WMI

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience


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