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

作　　者：Zhao-fu SHENG Xiang-yu CUI Su-ying CUI Bin 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 

机构地区：[1]Department of Pharmacology, School of Basic Medical Science, Peking University, Beijing 100191, China

出　　处：《Acta Pharmacologica Sinica》2015年第8期949-956,共8页中国药理学报（英文版）

摘　　要：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 weretreated with YH-200 （15, 30, and 60 m6/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 mEJkg） was more potent than the natural bisbenzylisoquinoline alkaloid tetrandrine （60 mg/kg） in FST. Pretreatment with al-adrenoceptor antagonist prazosin （1 mg/kg）, 13-adrenoceptor antagonist propranolol （2 mg/kg）, dopamine DiD5 receptor antagonist SCH23390 （0.05 mg/kg）, dopamine D2/D3 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 α2 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 αl, α2 and β-adrenoceptors, D1/D5 and D2/D3 receptors, as well as AMPA receptors.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 weretreated with YH-200 （15, 30, and 60 m6/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 mEJkg） was more potent than the natural bisbenzylisoquinoline alkaloid tetrandrine （60 mg/kg） in FST. Pretreatment with al-adrenoceptor antagonist prazosin （1 mg/kg）, 13-adrenoceptor antagonist propranolol （2 mg/kg）, dopamine DiD5 receptor antagonist SCH23390 （0.05 mg/kg）, dopamine D2/D3 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 α2 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 αl, α2 and β-adrenoceptors, D1/D5 and D2/D3 receptors, as well as AMPA receptors.

关 键 词：depression ANTIDEPRESSANT 7-O-ethylfangchinoline TETRANDRINE ADRENOCEPTOR dopamine receptor AMPA receptor forced swimming test tail suspension test 

分 类 号：TQ463.54[化学工程—制药化工] Q577[生物学—生物化学]