Involvement of adrenoceptors, dopamine receptors and AMPA receptors in antidepressant-like action of 7-O-ethylfangchinoline in mice-猫眼课题宝

DOI：

10.1038/aps.2015.57

发表时间：

2015-08

期刊：

影响因子：

通讯作者：

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其他

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作者：

Zhao-fu Sheng;Xiang-yu Cui;S. Cui;B. Yu;Xue-qiong Zhang;Sheng-jie Li;Qing Cao;Yuan-li Huang;Ya-ping Xu;Jin-zhi Song;Hui Ding;Zhi-ge Lin;Guang Yang;Yong-He Zhang

目的：7-O-乙基防己诺林（YH-200）是一种双苄基异喹啉衍生物。方法：在小鼠强迫游泳实验（FST）、悬尾实验（TST）和旷场实验（OFT）前，ig YH-200（15、30和60 mg/kg）或tetrandrine（30和60 mg/kg）。YH-200（60 mg/kg）对FST的作用强于天然双苄基异喹啉生物碱粉防己碱（60 mg/kg）。预先给予α 1受体拮抗剂哌唑嗪（1 mg/kg）、β受体拮抗剂普萘洛尔（2 mg/kg）、多巴胺D1/D5受体拮抗剂SCH 23390（0.05mg/kg）、多巴胺D2/D3受体拮抗剂氟哌啶醇（0.2mg/kg）或AMPA受体拮抗剂NBQX（10 mg/kg）可阻断YH-200（60 mg/kg）的抗抑郁作用。与此相反，预先给予α 2肾上腺素受体拮抗剂育亨宾（1 mg/kg）可增强YH-200（30 mg/kg）的抗抑郁作用。慢性给药YH-200（30和60 mg/kg，14天）没有产生耐药性，相反，其抗抑郁样作用得到加强。结论：YH-2 0 0对小鼠的抗抑郁作用是通过作用于α 1、α 2、β肾上腺素受体、D1/D5、D2/D3受体以及AMPA受体等多靶点发挥的

Aim:7-O-ethylfangchinoline (YH-200) is a bisbenzylisoquinoline derivative. The aim of this study was to investigate the antidepressant-like action and underlying mechanisms of YH-200 in mice.Methods:Mice were treated with YH-200 (15, 30, and 60 mg/kg, ig) or tetrandrine (30 and 60 mg/kg, ig) before conducting forced swimming test (FST), tail suspension test (TST), or open field test (OFT).Results:YH-200 (60 mg/kg) significantly decreased the immobility time in both FST and TST, and prolonged the latency to immobility in FST. YH-200 (60 mg/kg) was more potent than the natural bisbenzylisoquinoline alkaloid tetrandrine (60 mg/kg) in FST. Pretreatment with α 1-adrenoceptor antagonist prazosin (1 mg/kg), β-adrenoceptor antagonist propranolol (2 mg/kg), dopamine D 1/D 5 receptor antagonist SCH23390 (0.05 mg/kg), dopamine D 2/D 3 receptor antagonist haloperidol (0.2 mg/kg) or AMPA receptor antagonist NBQX (10 mg/kg) prevented the antidepressant-like action of YH-200 (60 mg/kg) in FST. In contrast, pretreatment with α 2 adrenoceptor antagonist yohimbine (1 mg/kg) augmented the antidepressant-like action of YH-200 (30 mg/kg) in FST. Chronic administration of YH-200 (30 and 60 mg/kg for 14 d) did not produce drug tolerance; instead its antidepressant-like action was strengthened. Chronic administration of YH-200 did not affect the body weight of mice compared to control mice.Conclusion:YH-200 exerts its antidepressant-like action in mice via acting at multi-targets, including α 1, α 2 and β-adrenoceptors, D 1/D 5 and D 2/D 3 receptors, as well as AMPA receptors.

Involvement of adrenoceptors, dopamine receptors and AMPA receptors in antidepressant-like action of 7-O-ethylfangchinoline in mice

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