阻断IKK/NF-κ B信号通路对大鼠恐惧记忆消退的影响

摘要

Objective To identify the role of the IKK / NF-kappa B signaling pathways in the acquisition and consolidation of extinction memory in conditioning fear.Methods Aduh SD rats were treated with nuclei buried surgery.After a week recovery from nuclei buried surgery,adult SD rats accepted auditory fear conditioning training.Before the extinction training,bilateral intra-BLA infusion of sulfasalazine(SSZ),an inhibitor of IKK/NFκ B,and Vehicle were done.The freezing time were tested on the 24h and 1w after the extinction.Results After training,all the rats showed higher percentage of freezing time than the baseline(Vehicle:pre-CS 21.16％,post-CS 71.23％,P＜0.01 ; SSZ:pre-CS 22.23％,post-CS 72.14％,P＜0.01).The percentage of freezing time had no significant difference(SSZ 47.52％,Vehicle 46.20％,P＞0.05)between Vehicle and SSZ at the end of extinction training.However,SSZ groups showed significantly higher percentage of freezing time than the control group on the 24h(Vehicle 41.03％,SSZ 60.51％,P＜0.01) and the same was found on 1 weck test(Vehicle 34.17％,SSZ 57.21％,P＜ 0.01).The rats injection with SSZ showed significant fear response for the auditory fear condition.Conclusion All above results suggest that interference of IKK/NF-κ B signaling pathway impaire the consolida tion but have no effect on the acquisition of fear extinction memory in conditioning fear.The available date could provide us some clinical guidance in the treatment of post-traumatic stress disorder and panic disorder.%目的 采用条件性恐惧记忆模型研究IKK/NF-κ B信号通路在大鼠听觉恐惧记忆消退获得及巩固阶段的影响.方法 成年SD大鼠接受BLA脑区核团埋管手术,术后恢复1周,进行听觉恐惧记忆训练.恐惧记忆建立后,消退训练前20 min,大鼠分别核团微注射IKK/NF-κ B的拮抗剂柳氮磺胺吡啶(SSZ)和生理盐水(Vehicle),然后进行消退记忆训练,分别在24 h和1周后进行恐惧记忆的行为学测试.结果 听觉恐惧记忆训练后,大鼠的僵住时间百分比明显增高(Vehicle组:pre-CS 21.16％,post-CS71.23％,P＜0.01；SSZ组:pre-CS 22.23％,post-CS 72.14％,P＜0.01)；听觉恐惧记忆消退训练前给予SSZ组和Vehicle组在消退训练结束时大鼠的僵住时间百分比无明显的差异(SSZ 47.52％,Vehicle 46.20％,P＞0.05),但是在训练结束后24 h的巩固测试中SSZ组大鼠的僵住时间百分比明显地高于Vehicle组(Vehicle41.03％,SSZ 60.51％,P＜0.01),而且1周后的长时程记忆的测试中SSZ组大鼠的僵住时间百分比也明显的高于Vehicle组(Vehicle 34.17％,SSZ 57.21％,P＜0.01),表现出明显的对条件性声音刺激的恐惧反应.结论 在听觉恐惧记忆的消退阶段,干扰大鼠BLA处IKK/NF-κ B信号通路的活性,破坏了消退记忆获得后的巩固,但对恐惧记忆消退的获得是没有影响的.结果提示IKK/NF-κ B信号通路可能在听觉恐惧记忆的消退过程中发挥着重要的作用,也为临床寻找消除PTSD药物治疗靶点提供理论依据.