Change of extinction retention and phosphorulated CREB in the rat infralimbic cortex after conditioned fear
AIM: To investigate the changes of extinction retention and expression of pCREB in rat's infralimbic cortex ( IL) at different regression time as well as at different time point after fear extinction. METHODS: Eighty male adult SD rats were randomly divided into control group (including conditioned fear group,shame A,B groups and normal control group),different regression time group(including natural extinction group,immediate extinction group and 24 h extinction group) and different time point after extinction group. Twenty-four hours fear extinction rats were randomly divided into extinction 1,3 and 7 d groups ( n = 8 ). The rats' conditioned fear was established by classical auditory fear con-ditioning(conditioned stimulus,CS) pairing with an aversive foot shock(unconditioned stimulus,US). Shame A and B groups were established by CS unpaired with US. Fear extinction training was performed with auditory indication but without foot shock in 15 min or 24 h after establishment of fear memory. Extinction retention test and expression of pCREB in IL were detected at 24 h after fear extinction and those in extinction 1,3 and 7 d groups were detected at 1st,3 rd and 7th day after extinction. The expressions of pCREB in IL were detected using immunohistochemistry and image analysis. RESULTS: The extinction retention ( % ) and expres- sion of pCREB in 24 h extinction group were better than those in natural extinction and immediate extinction groups [ ( 53 ± 12 ),(820 ± 106),P < 0. 01 ] and no statistical difference was found between natural extinction group and immediate extinction group. Shame A and B groups were lowest scored (20 ±7) and(22 ±6) and the expression of pCREB was most depressed (432 ± 97 ),(453 ±49),with no significant difference between groups. Compared with those in conditioned fear group,extinction retention scores and the number expression of pCREB in IL showed a gradual uptrend on 1st,3rd and 7th day after extinction (P < 0. 01 ). Compared with that in extinction 3 d group,difference between extinction 1 and 3 d groups was significant (P <0. 01 ). Compared with those in normal control group (87 ±7) and(994±31),the extinction retention and the expression of pCREB in IL in conditioned fear group remarkably decreased [ (37 ± 11),(692 ±60),P<0.01]. CONCLUSION: Expressions of pCREB in IL keep synchronized changes with the extinction retention score. Best effect is achieved in fear extinction 24 h after the establishment of conditioned fear. The 1st to the 3 rd day after the extinction may be the best therapeutic period.