The influence of anesthesia and surgery on fear extinction

Neurosci Lett. 2022 Jan 1;766:136347. doi: 10.1016/j.neulet.2021.136347. Epub 2021 Nov 19.


Accumulating evidence has demonstrated significant clinical post-traumatic stress disorder (PTSD) symptoms after anesthesia or surgery. Fear extinction dysfunction is a notable feature of PTSD. Although anesthetics and surgery profoundly affect memory processes, their designated effects on fear extinction have not been dissertated. Previous studies have suggested that innate immune system activation disrupts fear extinction, and surgery has been shown to increase the inflammatory response. Thus, in the current study, we examined the effects of propofol, sevoflurane, dexmedetomidine and surgery on fear extinction in adolescent mice, and further tested whether dexmedetomidine could reverse the injury effect of surgery on fear extinction through its anti-inflammatory effects. Our results showed that propofol (200 mg/kg) impaired the acquisition and recall of cued fear extinction, and surgery disrupted cued fear extinction acquisition/recall and consolidation. In contrast to cued fear extinction, contextual fear extinction was not affected by propofol or surgery. Moreover, dexmedetomidine prevented surgery-induced impairment of cued extinction acquisition and recall but not consolidation. Finally, TNF-α and IL-6 levels in the ventromedial prefrontal cortex were not necessary for the dexmedetomidine treatment effect of surgery-induced fear extinction dysfunction. The study results showed that propofol and surgery selective impaired the cued fear extinction stage in adolescent mice, and dexmedetomidine may unleash a protective effect in preventing postoperative PTSD.

Keywords: Anesthetics; Fear extinction; IL-6; Surgery; TNF-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia / adverse effects*
  • Anesthetics / adverse effects*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Dexmedetomidine / pharmacology
  • Extinction, Psychological / drug effects*
  • Fear*
  • Mental Recall / drug effects
  • Mental Recall / physiology
  • Mice
  • Propofol / adverse effects
  • Sevoflurane / adverse effects
  • Stress Disorders, Post-Traumatic / etiology
  • Surgical Procedures, Operative / adverse effects*


  • Anesthetics
  • Anti-Inflammatory Agents
  • Sevoflurane
  • Dexmedetomidine
  • Propofol