Post-reexposure administration of riluzole attenuates the reconsolidation of conditioned fear memory in rats
Post-reexposure administration of riluzole attenuates the reconsolidation of conditioned fear memory in rats
复制标题
再次暴露后给予利鲁唑可减弱大鼠条件性恐惧记忆的再巩固
DOI：
10.1016/j.neuropharm.2017.12.009
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发表时间：
2018
影响因子：
4.7
通讯作者：
M.
中科院分区：
文献类型：
--
作者：
Akagi;K.;Yamada;M.;Saitoh;A.;Oka;JI. and Yamada;M.
最近，我们证明了利鲁唑，它已经被证明可以阻断谷氨酸系统，促进老鼠的恐惧消退。本研究通过情境恐惧条件反射实验，阐明利鲁唑对大鼠恐惧记忆再巩固的作用。我们使用速效苯二氮卓类药物咪达唑仑作为再巩固抑制对照药物。我们证明利鲁唑（3mg /kg）和咪达唑仑（1mg /kg）损害了情境恐惧记忆的再巩固。自发恢复实验的结果也表明利鲁唑能减弱再巩固。事实上，条件恐惧在短时间（3分钟）再暴露和利鲁唑治疗4周后没有自发恢复，而在长时间（10分钟）再暴露后恢复。利用western blotting，我们证明了短时间的再暴露显著增加了海马背侧环腺苷单磷酸反应元件结合蛋白的磷酸化，但在内侧前额叶皮层没有。有趣的是，这种磷酸化作用被利鲁唑短时间的再暴露所减弱。此外，双侧直接向海马背侧注射利鲁唑（2 μM/0.2 μl/侧）可明显减弱再巩固。这些发现表明，利鲁唑对恐惧记忆再巩固的减弱作用至少部分涉及海马体的背侧。总之，我们证明了利鲁唑可以减弱大鼠恐惧记忆的再巩固。
Recently, we demonstrated that riluzole, which has been shown to block the glutamatergic system, facilitates fear extinction in rats. Here, we undertook experiments on contextual fear conditioning to clarify the actions of riluzole on the reconsolidation of fear memory in rats. We used the fast-acting benzodiazepine midazolam as a reconsolidation-inhibiting control drug. We demonstrated that riluzole (3 mg/kg) and midazolam (1 mg/kg) impaired the reconsolidation of contextual fear memory. Results from spontaneous recovery experiments also suggested that riluzole attenuated reconsolidation. Indeed, conditioned fear did not recover spontaneously 4 weeks after a short (3 min) reexposure and riluzole administration, whereas it recovered after a long (10 min) reexposure. Using western blotting, we demonstrated that a short reexposure increased the phosphorylation of cyclic adenosine monophosphate response element binding protein significantly in the dorsal part of hippocampus, but not in the medial prefrontal cortex. Interestingly, this phosphorylation was attenuated by riluzole with short reexposure. In addition, bilateral microinjection of riluzole (2 μM/0.2 μl/side) directly into the dorsal hippocampus clearly attenuated the reconsolidation. These findings suggested that the attenuating effect of riluzole on the reconsolidation of fear memory involves, at least in part, the dorsal part of the hippocampus. In conclusion, we demonstrated that riluzole attenuates the reconsolidation of fear memory in rats.