The Serotonergic Projection from the Median Raphe Nucleus to the Ventral Hippocampus is Involved in the Retrieval of Fear Memory Through the Corticotropin-Releasing Factor Type 2 Receptor
The Serotonergic Projection from the Median Raphe Nucleus to the Ventral Hippocampus is Involved in the Retrieval of Fear Memory Through the Corticotropin-Releasing Factor Type 2 Receptor
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DOI：
10.1038/npp.2009.229
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发表时间：
2010-05-01
影响因子：
7.6
通讯作者：
Yoshioka, Mitsuhiro
中科院分区：
文献类型：
--
作者：
Ohmura, Yu;Izumi, Takeshi;Yoshioka, Mitsuhiro
几项不同的研究分别证实了5-羟色胺、促肾上腺皮质激素释放因子（CRF）受体和海马体参与了恐惧记忆的提取。本研究的主要目的是将这些独立的研究联系起来。为了评估焦虑/恐惧的水平，我们分别使用情境恐惧条件反射测试和高架十字迷宫测试作为记忆依赖和记忆独立的任务。在行为测试前10分钟，我们将CRF受体拮抗剂或溶剂注射到中缝核（MRN）中。结果，1000 ng的astressin 2B（CRF 2受体拮抗剂），而不是250 ng的antalarmin（CRF 1受体拮抗剂），显着抑制表达率的冻结行为在上下文恐惧条件反射测试。然而，在高架十字迷宫试验中，注射astressin 2B的大鼠和注射盐水的大鼠在开放臂中花费的时间没有差异。无论是探索行为的数量，也不是在阿斯图里亚斯2B注射大鼠的大脑中的移动距离不同的溶剂注射的大鼠。此外，当我们通过体内微透析评估自由活动大鼠腹侧海马中细胞外5-羟色胺的释放时，结果表明，MRN中CRF 2受体的阻断抑制了恐惧记忆提取过程中腹侧海马中5-羟色胺的释放。这些结果表明，在MRN中释放的内源性CRF和/或相关配体可以激活CRF 2受体并刺激腹侧海马中的5-羟色胺释放，从而诱导恐惧记忆提取。Neuropsychopharmacology（2010）35，1271-1278; doi：10.1038/npp.2009.229; 2010年1月13日在线发表
Several different studies have separately established that serotonin, corticotropin-releasing factor (CRF) receptors, and the hippocampus are involved in fear memory retrieval. The main aim of this study is to connect these separate studies. To assess the levels of anxiety/fear, we used the contextual fear-conditioning test and the elevated plus maze test as memory-dependent and memory-independent tasks, respectively. We injected CRF receptor antagonists or vehicle into the median raphe nucleus (MRN) 10 min before behavioral tests. As a result, 1000 ng of astressin 2B (CRF2 receptor antagonist), but not 250 ng of antalarmin (CRF1 receptor antagonist), significantly suppressed the expression rate of freezing behavior in the contextual fear-conditioning test. However, in the elevated plus maze test, there was no difference between astressin 2B-injected rats and saline-injected rats in the time spent in open arms. Neither the amount of exploratory behavior nor the moving distance in the EPM of astressin 2B-injected rats differed from that of vehicle-injected rats. Moreover, when we assessed the extracellular serotonin release in the ventral hippocampus in freely moving rats through in vivo microdialysis, it was shown that the blockade of the CRF2 receptor in the MRN suppressed serotonin release in the ventral hippocampus during fear memory retrieval. These results indicated that endogenous CRF and/or related ligands that were released in the MRN could activate the CRF2 receptor and stimulate serotonin release in the ventral hippocampus, thereby inducing fear memory retrieval. Neuropsychopharmacology (2010) 35, 1271-1278; doi: 10.1038/npp.2009.229; published online 13 January 2010