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作 者:梁慧[1] 宫琦[1] 程涛[2] 梁建辉[1,2]
机构地区:[1]北京大学基础医学院药理学系,北京100191 [2]北京大学药学院分子与细胞药理学系,北京100191
出 处:《中国药理学与毒理学杂志》2017年第2期131-137,共7页Chinese Journal of Pharmacology and Toxicology
基 金:十二五科技支撑计划项目(2011BAK04B08)~~
摘 要:目的设计和建立梁氏情境应激箱,通过观察抗焦虑和抗抑郁药对小鼠行为学指标的影响,评价梁氏情境应激箱对小鼠焦虑和(或)抑郁样情绪反应的诱导作用。方法梁氏情境应激箱由中央区和3个外周臂构成。ICR小鼠分别ip给予抗焦虑药物丁螺环酮(0.5和1.0 mg·kg^(-1))和抗抑郁药物米安色林(0.25和0.5 mg·kg^(-1)),观察小鼠首次进入中央区的潜伏期、中央区停留时间、中央区活动路程、外周区活动路程、区域间穿梭次数和总活动度。结果 1丁螺环酮0.5和1.0 mg·kg^(-1)明显缩短小鼠首次进入中央区的潜伏期,分别缩短了71.9%(P<0.05)和77.9%(P<0.05);剂量依赖性地增加中央区停留时间,各增加了59.5%和73.8%(P<0.05);丁螺环酮0.5和1.0 mg·kg^(-1)均可显著减少小鼠区域间穿梭次数(P<0.05),但对其中央区活动路程、外周区活动路程和总活动度无明显影响;2米安色林0.25和0.5 mg·kg^(-1)明显缩短小鼠首次进入中央区的潜伏期,分别缩短了72.4%(P<0.05)和82.3%(P<0.05);剂量依赖性地增加中央区停留时间,各增加了39.1%和43.9%(P<0.05);米安色林剂量依赖性地增加中央区活动路程(P<0.05)及区域间穿梭次数(P<0.05),但对外周区活动路程和总活动度无明显影响。结论梁氏情境应激箱对小鼠焦虑和(或)抑郁样情绪反应具有明确的诱导作用,可作为一个新的焦虑抑郁共病动物模型研究其病理生理机制,筛选和评价新型抗焦虑和(或)抗抑郁药物。OBJECTIVE To investigate the effect of anxiolytics and antidepressants on anxietyand/or depression-like behaviours induced by designing a Liang′s contextual-stress box,(Liang′s box)in mice.METHODS Liang′s box was composed of a central area and three peripheral arms.Buspirone(0.5 and 1.0 mg·kg^-1) and mianserin(0.25 and 0.5 mg·kg^-1) were injected to mice intraperitoneally and the following behavioral indexes were recorded: ① latency to the central area(CA), ②CA-time, ③ CAdistance, ④ distance traveled in the peripheral area(PA-distance) 5 number of the transitions, and 6global activity.RESULTS ① Buspirone 0.5 and 1.0 mg·kg^-1 decreased the latency to CA by as much as 71.9%(P〈0.05) and 77.9%(P〈0.05), but dose-dependently increased the CA-time by 59.5% and73.8%(P〈0.05) respectively.Although buspirone 0.5 and 1.0 mg·kg^-1obviously reduced the shuttle number(P〈0.05), it did not have significant pharmacological effects on the CA-and PA-distance or global activity.② Mianserin 0.25 and 0.5mg·kg^-1decreased the latency to CA by as much as 72.4%(P〈0.05)and 82.3%(P〈0.05), but dose-dependently increased the CA-time by 39.1% and 43.9%(P〈0.05), respectively.Mianserin enhanced the shuttle number(P〈0.05) and CA-distance(P〈0.05) in a dose-dependent manner, but it had no obvious pharmacological effects on the PA-distance or global activity.CONCLUSION Anxiety-and/or depression-like behaviors can be stimulated by Liang′s box in mice, which may be used as a novel animal model of anxiety and depression comorbidity to study its pathophysiological mechanisms, screen and evaluate certain new anxiolytics and antidepressants.
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