Chronic treatment with fluoxetine prevents the return of extinguished auditory-cued conditioned fear
Chronic treatment with fluoxetine prevents the return of extinguished auditory-cued conditioned fear
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DOI：
10.1007/s00213-010-2134-y
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发表时间：
2011-05-01
影响因子：
3.4
通讯作者：
Garcia, Rene
中科院分区：
文献类型：
--
作者：
Deschaux, Olivier;Spennato, Guillaume;Garcia, Rene
理论基础我们最近发现，大鼠消亡后暴露在亚阈值提示电击下可以重新激活已熄灭的上下文相关冻结，并发现在恐惧消退之前使用氟西汀可以阻止这种现象。目的在本研究中，我们研究了这些发现是否会被听觉恐惧条件所证实。方法大鼠最初接受了5个音调电击配对的0.7 mA或0.1 mA电击，并在3天后接受了20个单音电击试验。结果在后一阶段的开始，我们观察到在接受强电击而不是弱电击的大鼠中出现了线索条件冻结。最后，两组(强电击和弱电击)显示出相似的低水平冰冻，这表明暴露在强电击下的大鼠的恐惧消失了。当这些大鼠暴露在三个音调电击配对的0.1毫安电击中时，它们再次表现出高水平的线索诱发的冰冻。这种线索条件性恐惧的重现被长期(持续21天)的氟西汀治疗完全消除，当氟西汀在最初的恐惧条件作用之前使用时，避免了原始的音调-电击联系。结论这些数据扩展了我们之前的发现，表明慢性氟西汀治疗通过抑制原始音调-电击联系的重新激活而有利于消退记忆。
Rationale We have recently shown that post-extinction exposure of rats to a sub-threshold reminder shock can reactivate extinguished context-related freezing and found that chronic treatment with fluoxetine before fear extinction prevents this phenomenon.Objectives In the present study, we examined whether these findings would be confirmed with auditory fear conditioning.Methods Rats were initially submitted to a session of five tone-shock pairings with either a 0.7- or 0.1-mA shock and underwent, 3 days later, a session of 20 tone-alone trials.Results At the beginning of this latter session, we observed cue-conditioned freezing in rats that received the strong, but not the weak, shock. At the end, both groups (strong and weak shocks) displayed similar low levels of freezing, indicating fear extinction in rats exposed to the strong shock. These rats exhibited again high levels of cue-evoked freezing when exposed to three tone-shock pairings with 0.1-mA shock. This reemergence of cue-conditioned fear was completely abolished by chronic (over a 21-day period) fluoxetine treatment which spared, when administered before the initial fear conditioning, the original tone-shock association.Conclusions These data extend our previous findings and suggest that chronic fluoxetine treatment favor extinction memory by dampening the reactivation of the original tone-shock association.