Norepinephrine Promote Persistence Of Long-term Context Fear Extinction

Objective：Life event has been considered leading to psychosis. Posttraumatic disorder (PTSD) and some other anxiety disorder that caused byhuge traumatic life event made people menticide and physiological functionbeing low down, breaking family relationship. PTSD could be imitated byanimal fear memory mode, exploring the mechanism of PTSD. Exposuretherapy is the most common psychological treatment of PTSD and anxietydisorder. After the training of the fear memory, the animal treating at the samecontext without shock for long time attenuated fear memory, which namedextinction and could be analogous exposure therapy. But fear memory couldbe recovered for reinstatement, renew and spontaneous recovery, suggestedthat the extinction is a new emotion memory. The consolidation of emotionalmemory could be promoted by noradrenaline (NE), expressed new gene andsynthetized new protein. It had been proved that PKA-CREB path way wasactivated by NE for promoting memory consolidation. So the experimenthypothesis that the late phase of consolidation (12h after the memoryacquisition) affect the persistence of the emotion memory, such as extinction,and could be promote by NE. The brain region of hippocampus CA1is veryimportant for emotion memory consolidation, for after acquisition, theconsolidation began with hippocampus CA1.Methods: The rats was first trained for context fear memory, thanextinction at the same context for30mins.12hs later, the rats was microinjectNE at hippocampus CA1region. The fear memory was tested at the2,14,15days after extinction, showed that NE could promote the persistence ofextinction at the14and15day, but not the2day. And microinjectedpropranolol or protease inhibitor Anisomycin ahead NE could block the effectof NE on extinction, pointed that the effect of NE was via β-receptor and had new protein synthesis.Results: Microinjection propranolol alone did not have any effect onextinction, presented that endogenous NE could affect extinction persistence.The late phase consolidation that influenced extinction long-term persistenceonly existed at12hs later, because immediately and6hs later microinjected NEcould not intervene in extinction. For the loco motor and anxiety sate alsoincreased rats freezing time, we tested loco motor and anxiety sate at the14day, showed no difference between NE group and saline group, remindedNE could not change the state of rat for long time.Conclusion: The long term persistence of extinction is one of the mostimportant research areas of PTSD treatment. The experiment presented theconsequence that NE could promote long term persistence of extinction whenmicroinjected at the later phase consolidation, supplied the basis forpreclinical research. It could improve the efficiency of exposure therapy,proved the extinction of fear memory was a new emotion memory and that thelater phase of consolidation was key for memory persistence.