Administration of riluzole to the basolateral amygdala facilitates fear extinction in rats
Administration of riluzole to the basolateral amygdala facilitates fear extinction in rats
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DOI：
10.1016/j.bbr.2017.08.031
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发表时间：
2018-01
影响因子：
2.7
通讯作者：
Azusa Sugiyama;M. Yamada;A. Saitoh;J. Oka;M. Yamada
中科院分区：
文献类型：
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作者：
Azusa Sugiyama;M. Yamada;A. Saitoh;J. Oka;M. Yamada
一般认为，基底外侧杏仁核（BLA）中的多巴胺能神经传递抑制会损害啮齿动物的恐惧消退。令人惊讶的是，我们最近发现，全身给药利鲁唑，这已被证明是抑制的mesamatergic系统，促进灭绝学习大鼠与预处理的背景恐惧反应。然而，利鲁唑这种矛盾作用的机制尚不清楚。在本研究中，成年雄性Wistar大鼠在BLA中双侧插管，以检查BLA内给予利鲁唑的影响。我们还比较了利鲁唑与d-环丝氨酸（一种N-甲基-d-天冬氨酸（NMDA）受体甘氨酸结合区的部分激动剂）的作用。在这项研究中，BLA内施用利鲁唑或环丝氨酸促进条件化大鼠对情境恐惧的消退学习。此外，利鲁唑和d-环丝氨酸在同一模型中均增强了再认记忆的获得。然而，BLA内注射利鲁唑，而不是环丝氨酸，有一个强大的抗焦虑样作用时，使用高架十字迷宫测试。我们的研究结果表明，利鲁唑诱导的促进消退学习的大鼠与预处理的背景恐惧反映了一种间接的影响，导致从内BLA管理的药物，并可能不直接相关的抑制amatergic信号。本研究中利鲁唑对恐惧消退学习的矛盾效应的机制还需要进一步的研究来阐明。
A general understanding exists that inhibition of glutamatergic neurotransmission in the basolateral amygdala (BLA) impairs fear extinction in rodents. Surprisingly, we recently found that systemic administration of riluzole, which has been shown to inhibit the glutamatergic system, facilitates extinction learning in rats with a preconditioned contextual fear response. However, the mechanisms underlying this paradoxical effect of riluzole remain unclear. In this study, adult male Wistar rats were bilaterally cannulated in the BLA to examine the effects of intra-BLA administration of riluzole. We also compared the effects of riluzole with those ofd-cycloserine, a partial agonist at the glycine-binding region of theN-methyl-d-aspartate (NMDA) receptor. In this study, intra-BLA administration of either riluzole ord-cycloserine facilitated extinction learning of contextual fear in conditioned rats. In addition, both riluzole andd-cycloserine enhanced the acquisition of recognition memory in the same model. However, intra-BLA injections of riluzole, but notd-cycloserine, had a potent anxiolytic-like effect when investigated using an elevated plus-maze test. Our findings suggest that riluzole-induced facilitation of extinction learning in rats with a preconditioned contextual fear reflects an indirect effect, resulting from the intra-BLA administration of the drug, and might not be directly related to inhibition of glutamatergic signaling. Further research is needed to clarify the mechanisms underlying the paradoxical effect of riluzole on fear extinction learning observed in this study.