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异丙酚麻醉损害恐惧记忆的巩固但不影响恐惧记忆的再巩固
Propofol could impair the consolidation of fear memory but not the reconsolidation of fear memory
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DOI:
作者:
尹骏 陆菡 马婧 薛庆生 曹晓华 张富军 于布为
Jun Yin, Han Lu, Jing Ma, Qingsheng Xue, Xiaohua Cao, Fujun Zhang, Buwei Yu
作者单位:
上海交通大学医学院附属瑞金医院
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
关键词:
异丙酚;记忆巩固;记忆再巩固
propofol; memory consolidation; memory reconsolidation
摘要:
目的 探究异丙酚麻醉对恐惧记忆巩固和再巩固的影响。 方法 实验包括两部分:异丙酚麻醉对恐惧记忆巩固的影响和异丙酚麻醉对恐惧记忆再巩固的影响。其中,异丙酚麻醉对恐惧记忆巩固的影响又可分为异丙酚麻醉剂量对恐惧记忆的影响及异丙酚麻醉时刻对恐惧记忆巩固的影响。在研究异丙酚麻醉剂量对恐惧记忆巩固的影响时,我们将32只成年雄性SD大鼠随机分为四组:N组,P100组,P150组,P200组;N组,P100组,P150组,P200组实验大鼠在场景恐惧实验训练结束后即刻分别接受腹腔注射生理盐水20ml/kg,异丙酚100mg/kg,异丙酚150mg/kg,异丙酚200mg/kg;24小时后进行恐惧记忆测试且在测试之前先进行开场实验。在研究异丙酚麻醉时刻对恐惧记忆巩固的影响时,我们将40只SD大鼠随机分为N0组,P0组,P1组,P2组,P3组。N0组实验大鼠在场景恐惧训练结束后即刻接受15ml/kg的生理盐水;P0组,P1组,P2组,P3组实验大鼠分别在场景恐惧训练结束后0h,1h,2h,3h接受腹腔注射150mg/kg异丙酚麻醉;24小时进行恐惧记忆测试,同样在测试之前先进行开场实验。在研究异丙酚麻醉对恐惧记忆再巩固的影响时,我们将24只成年雄性SD大鼠随机分为Nr组和Pr组;Nr组和Pr组大鼠分别在场景恐惧再现完成后即刻接受腹腔注射15ml/kg生理盐水或腹腔注射150mg/kg异丙酚;24小时后进行场景恐惧记忆测试,依然在测试之前先进行开场实验。 结果 各组实验大鼠在开场实验600s中的运动速度,运动距离,中央区时间均无统计学差异(P值均>0.05);在场景恐惧训练结束后即刻接受较高剂量(150mg/kg或200mg/kg)的异丙酚麻醉会损害场景恐惧记忆的巩固(P值均<0.05);在场景恐惧训练结束后1h,2h,3h接受150mg/kg的异丙酚麻醉均不会损害场景恐惧记忆的巩固。场景恐惧记忆再现完成后即刻接受150mg/kg异丙酚麻醉不会影响恐惧记忆的再巩固过程。 结论 以上结果表明,异丙酚麻醉可产生时间和剂量依赖性的损害恐惧记忆的巩固,但对恐惧记忆的再巩固无显著影响。
Objective To explore the effect of propofol on the consolidation and reconsolidation of fear memory. Methods In the first part, the effect of propofol on the consolidation of fear memory was studied. Adult male Sprague Dawley rats were trained in a contextual fear conditioning paradigm in which they received 3 foot shocks. Different doses (100mg/kg, 150mg/kg and 200mg/kg) of propofol were administered intraperitoneally immediately after training and propofol (150mg/kg) was administered intraperitoneally immediately or 1, 2, 3h after training. The retention was performed 24h later and the open field test was conducted before the retention. In the second part, we explored the effect of propofol on the reconsolidation of fear memory. Rats were returned to the conditioning chamber for 5 min in the absence of shock 24h after contextual fear conditioning (retrieval). Propofol (150mg/kg) was intraperitoneally immediately after retrieval. The retention was conducted 24h later and the open field test was performed before the retention. Results In the open field test, there was no difference in the speed, the distance and the time in the central area to different groups of rats. A higher dose of propofol administered immediately after training could significantly decrease the freezing time of context fear performance (37.58±2.49, 28.67±2.76, 150mg/kg and 200mg/kg, respectively; mean±SD) compared with the corresponding vehicle group (61.37±5.33, mean±SD). Delayed administration of propofol (150mg/kg) 1h, 2h and 3h could not significantly alter the retention. And propofol administered after context fear memory retrieval did not significantly change the retention either. Conclusions These findings indicate that propofol could impair the consolidation of fear memory but not the reconsolidation of fear memory.
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