Administration of a delta opioid receptor agonist KNT-127 to the basolateral amygdala has robust anxiolytic-like effects in rats
Administration of a delta opioid receptor agonist KNT-127 to the basolateral amygdala has robust anxiolytic-like effects in rats
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DOI：
10.1007/s00213-018-4984-7
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发表时间：
2018-10-01
影响因子：
3.4
通讯作者：
Yamada, Mitsuhiko
中科院分区：
文献类型：
--
作者：
Sugiyama, Azusa;Yamada, Misa;Yamada, Mitsuhiko
理论基础我们之前曾报道，选择性增量阿片受体(DOP)激动剂KNT-127的全身给药在大鼠身上产生了强大的抗焦虑作用。目的研究杏仁核内注射KNT-127对大鼠焦虑样行为的影响。方法与结果在高架+迷宫实验中，双侧杏仁核内注射KNT-127可显著增加大鼠在张开双臂中的活动时间，且呈剂量依赖关系。KNT-127(0.08mU g/0.2mU L)的抗焦虑作用强度与苍蝇酚(0.1mU g/0.2mU L)相似，后者是γ-氨基丁酸A受体的选择性激动剂。此外，KNT-127的抗焦虑作用可被DOP的选择性拮抗剂纳曲哚所消除，提示KNT-127的抗焦虑作用是由DOPS介导的。这些类似焦虑的作用通过另一种先天焦虑模型--旷场测试得到了证实。有趣的是，在背景恐惧条件反射测试中，白血球内注射KNT-127也产生了类似焦虑的效果。此外，这些作用也可被纳曲吲哚预处理所消除。总而言之，我们的发现清楚地表明，在大鼠的白质内注射KNT-127不仅在先天焦虑样行为测试中具有强大的抗焦虑作用，而且在情境恐惧条件反射测试中也具有强大的抗焦虑作用。
Rationale We previously reported that systemic administration of a selective delta opioid receptor (DOP) agonist, KNT-127, produced potent anxiolytic-like effects in rats. Interestingly, DOPs are highly distributed in the basolateral region of the amygdala (BLA).Objectives In this study, we investigated the effect of intra-BLA administration of KNT-127 on anxiety-like behaviors in rats.Methods and Results In the elevated plus maze test, bilateral injection of KNT-127 into the BLA significantly and dose-dependently increased time spent in the open arms. The magnitude of KNT-127 (0.08 mu g/0.2 mu l)-induced anxiolytic-like effects was similar to muscimol (0.1 mu g/0.2 mu l), which is a selective agonist for the gamma amino butyric acid type A receptors. Further, anxiolytic-like effects of KNT-127 were abolished by pretreatment with naltrindole, a selective DOP antagonist, suggesting that KNT-127-induced anxiolytic-like effects are mediated by DOPs. These anxiolytic-like effects were confirmed using another innate anxiety model, the open field test. Interestingly, intra-BLA administration of KNT-127 also induced anxiolytic-like effects in the contextual fear conditioning test. Moreover, these effects were also abolished by naltrindole pretreatment. Finally, we demonstrated that intra-BLA administration of KNT-127 facilitates extinction learning of contextual fear in conditioned rats.Conclusions Altogether, our findings clearly demonstrate that intra-BLA administration of KNT-127 in rats has robust anxiolytic-like effects not only in innate anxiety-like behavioral tests but also in the contextual fear conditioning test.