摘要
目的通过比较不确定性空瓶饮水刺激法和束缚应激法诱发小鼠产生焦虑样情绪,筛选一种重复性好、刺激性小且易于操作的方法建立小鼠焦虑模型,为寻找合适的抗焦虑药物的药效学评价模型提供实验依据。方法 SPF级雄性C57BL/6J小鼠采用不确定性空瓶饮水刺激法建立小鼠焦虑模型,实验分为自由饮水组、定时饮水组、生理应激组和空瓶刺激组,每组8只。自由饮水组小鼠全天自由进食饮水;定时饮水组小鼠每天固定2个时间点、间隔12 h,每次饮水10 min;在相同的时间点,生理应激组小鼠每天确保1次饮水10 min,另一次既不给水也不给空瓶;空瓶刺激组小鼠每天饮水时间随机给予1次或2次空瓶进行刺激,共计饮水12次,空瓶16次;实验持续14 d。采用束缚应激法建立小鼠焦虑模型,实验分为正常对照组和束缚应激组,每组8只。正常对照组小鼠正常饲养,束缚应激组小鼠于每天早上9∶00头朝离心管的底部束缚在管内,第1天束缚2 h,随后每天束缚时间延长2 h,直至每天8 h,连续21 d。小鼠在空瓶刺激7和14 d后或束缚应激7,14和21 d后观察体质量的变化。造模结束后,通过旷场实验检测小鼠自主活动和探索行为,高架十字迷宫实验检测小鼠进入开放臂的次数和在开放臂内停留时间;采用ELISA测定束缚应激21 d后小鼠血浆皮质酮(CORT)水平和海马组织中5-羟色胺(5-HT)含量。结果不确定性空瓶饮水刺激法:与自由饮水组相比,定时饮水组小鼠在开放臂内停留时间显著下降(P<0.05);与定时饮水组相比,空瓶刺激7 d后,小鼠体质量显著下降(P<0.05),其他各项行为学指标无明显变化。束缚应激法:与正常对照组相比,束缚应激14 d后,小鼠体质量显著降低(P<0.05),小鼠的自主活动和探索行为无明显变化,进入开放臂的次数和在开放臂内停留时间均显著下降(P<0.05);束缚应激21 d后,小鼠体质量显著降低(P<0.05),血浆CORT含�
OBJECTIVE To screen a mouse anxiety model with good reproducibility, little stimulation and user-friendliness by comparing the uncertain empty bottle drinking water stimulation with restraint stress to induce anxiety-like emotion in mice in order to find a suitable pharmacodynamic evaluation model for anti-anxiety drugs which provides an experimental basis. METHODS A mouse anxiety model was established using the uncertain empty bottle drinking water stimulation method. The mice were divided into freely drinking water group, regular drinking water group, physiological stress group and empty bottle stimulation group, with eight mice in each group. The freely drinking water group was free to eat and drink all day, the regular drinking water group mice were given free water for 2 periods per day, while the regular drinking water group mice were given water for 10 min at 2 fixed time with a 12 h interval every day. At the same time, physiological stress group mice had access to drinking water for 10 min once a day, but at another time they were given neither water nor empty bottles. The empty bottle stimulation group mice were given empty bottle stimulation randomly once or twice every day so that they drank water 12 times and empty bottle stimulation 16 times. The experiment lasted 14 d. The mouse anxiety model was established with restraint stress method. The experimental mice were divided into normal control group and restraint stress group, with eight mice in each group. The normal control group was normally reared, while the restraint stress group mice were confined to the tube at 9∶00 every morning,headed towards the bottom of the centrifuge tube and were restrained for 2 h on the first day, and then the daily binding strength was extended for 2 h until 8 h every day for 21 d. The changes of body mass in mice after 7 and 14 d of empty bottle stimulation and after 7, 14, and 21 d of restraint stress were observed. At the end of the modeling, the mice were tested for autonomous activities and exploration behavio
作者
朱明好
蒋宁
周文霞
ZHU Ming-hao;JIANG Ning;ZHOU Wen-xia(Graduate School,Nanjing University of Chinese Medicine,Nanjing 210023,China;Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;State Key Laboratory of Toxicology and Medical Countermeasure,Beijing 100850,China)
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2019年第2期102-108,共7页
Chinese Journal of Pharmacology and Toxicology
关键词
空瓶刺激
束缚应激
焦虑
empty bottle stimulation
restraint stress
anxiety
