The Influence Of Anesthesia And Surgery On Fear Memory Extinction

Background: Post-traumatic Stress Disorder（PTSD）is a late onset and persistent psychological Disorder that occurs after an individual experiences a severe traumatic event,which tends to occur in adolescence.The long-term retention of fear memory is an important mechanism of PTSD.It is closely related to the enhancement of fear memory and the weakening of fear extinction.The gold standard for PTSD treatment is exposure therapy based on the theory of fear extinction.Clinical evidence suggests that approximately 20% of patients have significant PTSD symptoms after surgery,but the mechanism of occurrence is unclear.Previous studies have shown that anesthesia and surgery can lead to postoperative cognitive changes by affecting the acquisition,consolidation,and recall,but the effect of anesthesia and surgery on fear extinction is unclear.It is worth considering whether PTSD symptoms after surgery are caused by fear memory extinction disorder.In addition,studies have shown that inflammation can lead to fear extinction disorder,while surgery can lead to severe inflammation.Therefore,we speculate that surgery may lead to fear memory extinction disorder through inflammation,and then lead to postoperative PTSD.In addition,Dexmedetomidine has been found to have significant anti-inflammatory effects.We hypothesized that dexmedetomidine might alleviate the fear extinction disorder after surgery through its anti-inflammatory effect.In conclusion,we intend to observe the effects of propofol,sevoflurane,dexmedetomidine and surgery on fear extinction in adolescent mice,and further explore whether the anti-inflammatory effect of dexmedetomidine can alleviate the post-surgical fear memory extinction disorder.Methods:First,to determine the effects of anesthesia on the acquisition and consolidation of fear extinction in adolescent mice,C57BL/6 mice aged 28-30 days were selected and divided into two parts.And then randomly divided into control group,propofol group（200mg/kg）,sevoflurane group（2%,2h）,dexmedetomidine group（40μg/kg）.Each group contained 14 mice.In the first part,the mice were treated with drugs after fear conditioning training,and the freezing behavior was observed at the stage of cued or contextual extinction memory acquisition and recall.The other mice were treated with rugs immediately after fear extinction training,and the freezing behavior in the extinction recall was observed.Second,in order to determine the effect of surgery on fear memory extinction and the effect of dexmedetomidine on fear memory extinction in surgical mice,C57BL/6 mice aged 28-30 days were divided into two parts.And then randomly divided into control group,surgery group,surgery +dexmedetomidine group.In the first part,the mice were treated with surgery or drug after fear condition training to observe the freezing behavior in the acquisition and recall stage of extinction.The other part of the mice underwent surgery or drug just after the acquisition of extinction memory,and the freezing behavior in the recall of extinction memory was observed.Finally,TNF-α and IL-6 levels in ventral medial prefrontal cortex（vm PFC）were detected.Results: Our results showed that propofol-injected mice exhibited more freezing time during the cued fear extinction acquisition and extinction recall compared with control mice.Surgery group mice exhibited more freezing behavior during the cued fear extinction acquisition and extinction recall compared with control group and surgery +dexmedetomidine group.Moreover,surgery mice showed much more freezing behavior when acclimatizing in the extinction recall stage.However,there was no significant difference in freezing behavior between the surgery mice and the surgery +dexmedetomidine mice.Finally,the levels of TNF-α and IL-6 in vm PFC were not significantly changed in each group.Conclusions: Propofol impaired cued fear memory extinction training and memory retention after training in adolescent mice,surgery induced cued fear memory extinction disorder in adolescent mice,and dexmedetomidine alleviated the cued fear memory extinction disorder after surgery.