Communications Biology (Jul 2023)

A prolonged stress rat model recapitulates some PTSD-like changes in sleep and neuronal connectivity

  • Yun Lo,
  • Pei-Lu Yi,
  • Yi-Tse Hsiao,
  • Tung-Yen Lee,
  • Fang-Chia Chang

DOI
https://doi.org/10.1038/s42003-023-05090-9
Journal volume & issue
Vol. 6, no. 1
pp. 1 – 19

Abstract

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Abstract Chronic post-traumatic stress disorder (PTSD) exhibits psychological abnormalities during fear memory processing in rodent models. To simulate long-term impaired fear extinction in PTSD patients, we constructed a seven-day model with multiple prolonged stress (MPS) by modifying manipulation repetitions, intensity, and unpredictability of stressors. Behavioral and neural changes following MPS conveyed longitudinal PTSD-like effects in rats for 6 weeks. Extended fear memory was estimated through fear retrieval induced-freezing behavior and increased long-term serum corticosterone concentrations after MPS manipulation. Additionally, memory retrieval and behavioral anxiety tasks continued enhancing theta oscillation activity in the prefrontal cortex-basal lateral amygdala-ventral hippocampus pathway for an extended period. Moreover, MPS and remote fear retrieval stimuli disrupted sleep-wake activities to consolidate fear memory. Our prolonged fear memory, neuronal connectivity, anxiety, and sleep alteration results demonstrated integrated chronic PTSD symptoms in an MPS-induced rodent model.