4-AP对小鼠恐惧记忆形成的影响

EFFECT OF 4-AMINOPYRIDINE ON FEAR MEMORY FORMATION IN MICE

目的了解4-氨基吡啶(4-AP)对成年及老年C57Bl6J野生型小黑鼠条件性恐惧记忆形成的影响及其可能机制。方法采用场景前置性条件恐惧记忆测试、条件性场景恐惧记忆测试及条件性声音恐惧记忆测试3种行为学模型,检测老年及成年C57Bl6J野生型小鼠急性腹腔注射4-AP(1mg/kg)后对各场景恐惧反应,以生理盐水腹腔注射作为对照组,用僵直时间占总测试时间的百分比(僵直时间%)来表示小鼠的恐惧程度。结果在场景前置性条件恐惧记忆测试中,足底电击24h后,老年小鼠和成年小鼠的僵直时间%差异有显著性(t=3.32,P<0.01);4-AP急性腹腔注射后,对照组和实验组老年小鼠的僵直时间%差异有显著性(t=2.94,P<0.05),对照组和实验组成年小鼠僵直时间%差异无显著性(P>0.05)。在条件性场景恐惧记忆测试及条件性声音恐惧记忆测试中,4-AP急性腹腔注射后,在短期恐惧记忆(30min)及长期恐惧记忆(24h)测试中,对照组和实验组老年小鼠的僵直时间%差异无显著性(P>0.05)。结论老年小鼠不能形成对场景前置的恐惧记忆,应用4-AP可在一定程度上改善衰老引起的认知障碍。

Objective To study the possible effect and mechanisms of 4-aminopyridine （4-AP） on conditioning fear memory （CFM） formation in adult and aged C57Bl6J mice. Methods Using three kinds of ethological models-pre-exposure conditioning fear memory test （PECFMT）, contextual fear conditioning （CFC） and auditory fear conditioning （AFC）-the fear reactions in the experimental mice after peritoneal injection of 4-AP （1 mg/kg） to each scene were recorded, those peritoneal injection of nromal saline served as controls. The extent of fear was demonstrated by percentage of freezing time/total testing time （freezing time%）. Results In PECFMT, the difference of percentage of freezing time between adult and aged mice 24 h after foot-sole electric shock was significant （t=3.32,P〈0.01）. Significant freezing time difference was also observed in aged mice treated by 4-AP administration compared to the control group （t=2.94,P〈0.05）, but the difference of that between adult mice was not significant （P〉0.05）. In CFC and AFC tests, after rapid peritoneal injection of 4-AP, the differences of freezing time of the aged mice between the control and experimental groups were not significant in terms of short-term （30 min） and long-term （24 h） fear memory （P〉0.05）. Conclusion Pre-exposure conditioning fear memory is unable to be formed in aged mice, the application of 4-AP may to a certain degree improve cognition caused by aging.