Selective agonists of the δ-opioid receptor, KNT-127 and SNC80, act differentially on extinction learning of contextual fear memory in mice
Selective agonists of the δ-opioid receptor, KNT-127 and SNC80, act differentially on extinction learning of contextual fear memory in mice
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δ-阿片受体的选择性激动剂 KNT-127 和 SNC80 对小鼠情境恐惧记忆消退学习的作用不同
DOI：
10.1016/j.neuropharm.2019.107792
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发表时间：
2019
影响因子：
4.7
通讯作者：
Akiyoshi Saitoh
中科院分区：
文献类型：
--
作者：
DaisukeYamada,Shoko Yanagisawa;Kazumi Yoshizawa;Shinya Yanagita;Jun-Ichiro Oka;Hiroshi Nagase;Akiyoshi Saitoh
我们以前报道过，KNT-127和SNC 80，δ-阿片受体（DOP）的选择性激动剂，在啮齿动物中具有有效的抗焦虑样作用。在本研究中，我们评估了KNT-127和SNC 80是否影响小鼠恐惧条件化实验中情境恐惧记忆的消退学习。在第1天，用8次试验（足电击; 0.8mA，1秒，30秒间隔）对小鼠进行情境条件反射。在第2天，在给药后30分钟，将小鼠再次暴露于调节室6分钟作为消退训练（再次暴露1）。在第3天，将小鼠再次暴露于室中6分钟作为记忆测试（再次暴露2）。在再暴露1中，KNT-127和SNC 80显著降低冻结行为。在再暴露2中，KNT-127而不是SNC 80显著降低了冻结行为。KNT-127的这些作用可被DOP拮抗剂纳曲吲哚拮抗。KNT-127增加了杏仁核和海马中磷酸化ERK的水平，但在再次暴露后60分钟，内侧前额叶皮质中没有增加。这些结果表明，KNT-127和SNC 80在再暴露1中都产生了抗焦虑样作用，然而，与SNC 80相反，KNT-127在再暴露2中促进了背景恐惧记忆的消退学习。此外，我们认为杏仁核和海马MAPK/ERK信号通路是KNT-127处理后通过DOP增强背景恐惧记忆消退学习的关键介质。我们提出，虽然DOP激动剂KNT-127和SNC 80产生抗焦虑的效果，上下文条件性恐惧，这些药物有不同的机制，对上下文恐惧记忆的消退学习。
We reported previously that KNT-127 and SNC80, selective agonists of the δ-opioid receptor (DOP), had potent anxiolytic-like effects in rodents. In this study, we evaluated whether KNT-127 and SNC80 influence extinction learning of contextual fear memory in the mice fear conditioning test. On day 1, the mice were contextually conditioned with eight trials (footshock; 0.8 mA, 1-s, 30-s interval). On day 2, the mice were re-exposed to the conditioning chamber for 6 min as an extinction training (re-exposure 1), 30 min after drug administration. On day 3, the mice were re-exposed to the chamber for 6 min as a memory testing (re-exposure 2). In re-exposure 1, KNT-127 and SNC80 significantly reduced the freezing behavior. In re-exposure 2, KNT-127, but not SNC80, significantly reduced the freezing behavior. These effects of KNT-127 were antagonized by the DOP antagonist naltrindole. KNT-127 increased the phosphorylated ERK levels in the amygdala and hippocampus, but not in the medial prefrontal cortex 60 min after re-exposure 1. These results suggest that both KNT-127 and SNC80 produced anxiolytic-like effects in the re-exposure 1, however, in contrast to SNC80, KNT-127 facilitated extinction learning of contextual fear memory in the re-exposure 2. Further, we suggest that amygdaloid and hippocampal MAPK/ERK signaling serves as the key mediators of the enhancement of extinction learning of contextual fear memory via DOPs after KNT-127 treatment. We propose that, although the DOP agonists KNT-127 and SNC80 produce anxiolytic-like effects on contextually conditioned fear, these drugs have different mechanisms on extinction learning of contextual fear memory.
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影响因子：
3.5
作者：
F. Sananbenesi;A. Fischer;Christina Schrick;J. Spiess;J. Radulovic
通讯作者：
F. Sananbenesi;A. Fischer;Christina Schrick;J. Spiess;J. Radulovic
DOI：
10.1523/jneurosci.3842-06.2007
发表时间：
2007-01
期刊：
The Journal of Neuroscience
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影响因子：
3.4
作者：
Sugiyama, Azusa;Yamada, Misa;Yamada, Mitsuhiko
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影响因子：
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作者：
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通讯作者：
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