Hippocampal neurogenesis mediates sex-specific effects of social isolation and exercise on fear extinction in adolescence

Katherine D. Drummond, Michelle L. Waring, Geoffrey J. Faulkner, Marnie E. Blewitt, Christina J. Perry, Jee Hyun Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
45 Downloads (Pure)


Impaired extinction of conditioned fear is associated with anxiety disorders. Common lifestyle factors, like isolation stress and exercise, may alter the ability to extinguish fear. However, the effect of and interplay between these factors on adolescent fear extinction, and the relevant underlying neural mechanisms are unknown. Here we examined the effects of periadolescent social isolation and physical activity on adolescent fear extinction in rats and explored neurogenesis as a potential mechanism. Isolation stress impaired extinction recall in male adolescents, an effect prevented by exercise. Extinction recall in female adolescents was unaffected by isolation stress. However, exercise disrupted extinction recall in isolated females. Extinction recall in isolated females was positively correlated to the number of immature neurons in the ventral hippocampus, suggesting that exercise affected extinction recall via neurogenesis in females. Pharmacologically suppressing cellular proliferation in isolated adolescents using temozolomide blocked the effect of exercise on extinction recall in both sexes. Together, these findings highlight sex-specific outcomes of isolation stress and exercise on adolescent brain and behavior, and highlights neurogenesis as a potential mechanism underlying lifestyle effects on adolescent fear extinction.

Original languageEnglish
Article number100367
Pages (from-to)1-16
Number of pages16
JournalNeurobiology of Stress
Publication statusPublished - Nov 2021
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • stress
  • sex differences
  • adolescence
  • exercise
  • neurogenesis


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