The Effect Of NR2B, BDNF And Caspase-3 In The Extinction Retention Of Conditioned Fear Memory In Infralimbic Cortex Of Rats

Background: Recently, with increasing of sudden catastrophic events (earthquake, flood, terrorist attack etc) post-traumatic stress disorder (PTSD) has received much attention. PSTD is an anxiety disorder developed after exposuring to traumatic events and characterized by a series of physical or psychological response. Once the traumatic memories formed, it is very difficult to vanish and give patients great suffering. At present, the exposure therapy is commonly used in the treatment of PTSD, but about 40% of the patients had the tendency to relapse. This suggests that retention disorder of extinction memory maybe the key factor in the occurrence and treatment of PTSD. So research on the retention of extinction memory is very important.Fear extinction is that when the conditioned stimulus(CS) repeatedly present without unconditioned stimulus (US, such as foot shock) paired,the conditioned fear response becomes weaken or disappeared. It does not mean the erasing of the previously formed CS-US association memory, but forming a CS- no US memory (extinction memory). A large number of studies have shown that IL of mPFC involved in fear conditioning process and is a site to store the extinction memory. However, it is not clear which substances involved in the process of fear extinction.Based on the previous studies, we used behavioral, morphological and Western Blot methods to study the mechanism of fear extinction retention in IL of mPFC.Objective: This study aims to investigate the dynamic changes of NR2B and BDNF and caspase-3 in IL of mPFC after fear extinction training.Method: 75 SD rats were randomly divided into 3 groups:control group(receiving no fear and extinction training, Cont ),24h extinction group (receiving fear and extinction training, EXT)and non-extinction group(receiving fear but no extinction training, N-EXT).Conditioned fear was established with CS (classical auditory fear conditioning) pairing with unconditioned stimulus (aversive foot shock). 24h after the conditioned fear, the extinction group were given extinction training. Freezing behavioral and the NR2B, BDNF and caspase-3 in IL of mPFC were assessed.Result:1. Retention of extinction memory:After fear extinction training, the score of extinction retention increased with time. EXT group have a significant higher score than N-EXT group on the 3rd and 7th day (p<0.01)2. NR2B, BDNF immunoreactive positive substance in IL area:The amount of NR2B and BDNF immunoreactive positive substance increased with time in N-EXT group and EXT group but lower than Control group. There was a rapid change from 1st day to 3rd day and reach maximum on the 7th day (p>0.01). The positive expression value of NR2B and BDNF in N-EXT rats is lower than that in EXT group and control group.3. Caspase-3 immunoreactive positive substance in IL area:Comparing with control group: (1) The amount of caspase-3 in N-EXT group and EXT group is higher than that in control group. (2) After extinction training, the amount of caspase-3 in EXT group decreased with time and almost returned to normal at 7th days after extinction.Conclusion:(1) Extinction training is helpful to reduce conditioned fear memory. So it is necessary for PTSD patients to have exposure therapy.(2) NR2B and BDNF in IL area might play important roles in retention of fear extinction memory.(3) NR2B, BDNF and Caspase-3 in IL area may participate in the plasticity during the retention of fear extinction memory. But the mechanism need to be further studied.