摘要
目的通过单次皮下注射不同剂量皮质酮模拟不同程度急性应激刺激,并评价小鼠情绪症状与认知功能的变化,拟建立一种稳定可靠的急性应激障碍(ASD)模型。方法SPF级BALB/c小鼠经自主活动性筛选后,按自主活动及体质量随机分为对照组、皮质酮给药组(50、100和200 mg/kg)。行为学实验均在皮质酮注射1 h后进行。采用旷场实验、高架十字迷宫实验和悬尾实验评价单次皮质酮注射对小鼠情绪症状的影响;采用新物体识别实验和Morris水迷宫实验评价单次皮质酮注射对小鼠认知功能的影响。结果与对照组相比,皮质酮50 mg/kg组小鼠情绪及认知行为无明显改变。皮质酮100 mg/kg可使小鼠在旷场实验中中心区域进入时间从(17.99±2.80)s降低为(6.36±1.98)s(P<0.05),中心区域进入次数从(13.80±1.76)次降低为(7.22±1.72)次(P<0.01);对高架十字迷宫的开放臂进入时间和次数及悬尾实验的不动时间无明显影响;小鼠对新物体的偏好指数从0.56±0.06降低为0.37±0.04(P<0.05);水迷宫实验中小鼠的目标象限停留时间从(31.53±3.51)s降低为(18.55±2.98)s(P<0.05),目标象限运动距离从(4.82±0.43)m降低为(2.69±0.38)m(P<0.01)。当皮质酮剂量达到200 mg/kg时小鼠在旷场中活动的总距离从(16.98±1.15)m降低为(11.72±1.48)m。结论单次皮下注射100 mg/kg皮质酮可诱导类ASD症状,出现焦虑样精神障碍,物体识别记忆和空间记忆等认知功能损伤,可作为一种稳定可靠的ASD动物模型用于抗ASD药物的筛选和相关机制研究。
Objective To establish a stable and reliable model of acute stress disorder(ASD)via subcutaneous injection of corticosterone in mice.Methods SPF BALB/c mice were randomly divided into control and corticosterone-treated groups(50,100,and 200 mg/kg)according to their spontaneous activity and body mass.Different doses of corticosterone were administered via single subcutaneous injection to mimic acute stress.Behavioral tests were performed 1 hour after corticosterone injection.The effects of corticosterone on the emotional symptoms were evaluated by open field test,elevated plus maze test and tail suspension test.Novel object recognition test and Morris water maze test were used to evaluate the cognitive function.Results Compared with the control group,50 mg/kg corticosterone did not cause significant changes in emotional and cognitive behavior.In the 100 mg/kg corticosterone group,the center zone time decreased significantly from(17.99±2.80)s to(6.36±1.98)s(P<0.05)and the center zone entries decreased significantly from 13.80±1.76 to 7.22±1.72(P<0.01)in open field test,but there were few changes in the elevated plus maze test and tail suspension test.For cognitive behaviors,the preference index in novel object recognition test decreased significantly from 0.56±0.06 to 0.37±0.04(P<0.05);time in the target quadrant decreased significantly from(31.53±3.51)s to(18.55±2.98)s(P<0.05)and distance in the target quadrant decreased significantly from(4.815±0.430)m to(2.687±0.381)m(P<0.01)in Morris water maze test.When the corticosterone reached 200 mg/kg,the total distance of mice in the open field decreased significantly from(16.98±1.15)m to(11.72±1.48)m.Conclusion A single subcutaneous injection of 100 mg/kg corticosterone induced similar symptoms of ASD:anxiety-like disorders and learning&memory impairment.This study provides a mouse model for the ASD related mechanism studies and anti-ASD drug screening.
作者
路畅
王陈
周文霞
黄晏
张永祥
LU Chang;WANG Chen;ZHOU Wen-xia;HUANG Yan;ZHANG Yong-xiang(School of Pharmaceutical Sciences,Yantai University,Yantai 264005,China;State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)
出处
《国际药学研究杂志》
CAS
北大核心
2020年第4期276-282,289,共8页
Journal of International Pharmaceutical Research
基金
国家“重大新药创制”科技重大专项资助项目(2016ZX09J16104-001)
植物化学与西部植物资源持续利用国家重点实验室开放课题(P2017-KF13)。
关键词
皮质酮
急性应激障碍
焦虑
认知损伤
corticosterone
acute stress disorder
anxiety
cognitive impairment
