Small-molecule non-peptide antagonists of the PACAP receptor attenuate acute restraint stress-induced anxiety-like behaviors in mice
Small-molecule non-peptide antagonists of the PACAP receptor attenuate acute restraint stress-induced anxiety-like behaviors in mice
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PACAP 受体的小分子非肽拮抗剂可减轻小鼠急性束缚应激诱导的焦虑样行为
DOI：
10.1016/j.bbrc.2022.09.079
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发表时间：
2022
影响因子：
3.1
通讯作者：
Hashimoto Hitoshi
中科院分区：
文献类型：
--
作者：
Shintani Yusuke;Hayata-Takano Atsuko;Yamano Yui;Ikuta Mankato;Takeuchi Rei;Takuma Kazuhiro;Okada Takuya;Toyooka Naoki;Takasaki Ichiro;Miyata Atsuro;Kurihara Takashi;Hashimoto Hitoshi
腺苷酸环化酶激活多肽（PACAP）是一种高度保守的多效性神经肽，参与情绪应激反应和焦虑相关疾病。在这里，我们研究了我们最近开发的小分子非肽PACAP受体拮抗剂是否可以改善小鼠急性束缚应激诱导的焦虑样行为。拮抗剂PA-9及其衍生物PA-915改善了束缚应激小鼠的焦虑样行为。单次急性给药观察到抗焦虑作用，表明其速效特性。PA-915表现出具有统计学显著性的抗焦虑作用，而氟西汀则无此作用。这些结果表明，PAC 1拮抗剂作为一种新的治疗焦虑症的潜力。
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide, implicated in emotional stress responses and anxiety-related disorders. Here, we examined whether our recently developed small-molecule non-peptide PACAP receptor antagonists could ameliorate anxiety-like behaviors induced by acute restraint stress in mice. The antagonists PA-9 and its derivative PA-915 improved anxiety-like behaviors in mice subjected to restraint stress. An anxiolytic effect was observed with single acute dose, suggesting their fast-acting properties. PA-915 demonstrated a statistically significant anxiolytic effect whereas fluoxetine did not. These results indicate the potential of PAC1 antagonists as a novel treatment for anxiety.