2种小鼠应激模型致模式分离损伤特点及米非司酮和普萘洛尔对足底电击模型小鼠模式分离的干预作用比较

Characteristics of influence of two different mouse stress models on pattern separation and comparison of interventions by mifepristone and propranolol

目的比较2种小鼠应激模型致模式分离损伤的特点及米非司酮和普萘洛尔的干预作用。方法①分别采用足底电击或sc注射给予皮质酮(50和100 mg·kg^(-1))2种方式制备小鼠应激模型,采用物体识别范式评价应激后第1,8和15天小鼠时间与空间模式分离能力;②在足底电击模型上,C57BL/6J小鼠按体重和自主活动性随机分为正常对照组、足底电击组、足底电击+米非司酮(70 mg·kg^(-1))组、足底电击+普萘洛尔(20 mg·kg^(-1))组和足底电击+米非司酮+普萘洛尔组。每次足底电击应激前30 min ip给药,观察小鼠的时间和空间模式分离能力。结果①在足底电击模型上,与正常对照组相比,造模后第1天模型组小鼠的时间辨别指数及空间辨别指数均显著降低(P<0.05);第8天仅空间辨别指数明显降低(P<0.01);第15天时间及空间辨别指数均无明显差异。在sc注射皮质酮模型中,与正常对照组比较,模型组小鼠仅于造模后第1天表现出空间辨别指数显著降低(P<0.05),造模第8和15天,空间与时间辨别指数均未见显著变化。②足底电击应激前给予米非司酮可显著提高足底电击模型小鼠的空间辨别指数(P<0.05),给予普萘洛尔则显著提高时间辨别指数(P<0.05),两药联用可显著提高时间和空间辨别指数(P<0.05)。结论足底电击应激对空间和时间模式分离均有损伤作用,外源性皮质酮注射应激仅造成空间模式分离损伤;米非司酮对空间模式分离损伤具有改善作用,而普萘洛尔对时间模式分离损伤具有改善作用,两药联用对时间和空间模式分离损伤均有显著改善作用。

OBJECTIVE To compare the characteristics of pattern separation deficits in two different mouse stress models and explore the intervention effects of mifepristone and propranolol.METHODS①The stress model was established by two means:foot-shock and subcutaneous injection of corticosterone(50 and 100 mg·kg^(-1)).The mice's ability of temporal and spatial pattern separation was evaluated based on the object recognition paradigm on the 1^(st),8^(th) and 15^(th) day after stress.②In the foot-shock model,C57BL/6J mice were randomly divided into the normal control group,foot-shock group,mifepristone group(70 mg·kg^(-1)),propranolol group(20 mg·kg^(-1))and mifepristone combined with propranolo group.Mifepristone and propranolol were administered via intraperitoneally injection 30 min before each stress,and the temporal and spatial discrimination indexes were observed.RESULTS①In the foot-shock model,the temporal and spatial discrimination indexes decreased significantly on the 1^(st) day after modeling compared with the normal control group(P<0.05).On the 8^(th) day,only the spatial discrimination index decreased significantly(P<0.01).There was no significant difference in temporal or spatia discrimination indexes on the 15^(th) day.In the exogenous corticosterone injection model,the spatial discrimination indexes of model mice decreased significantly only on the 1^(st) day after modeling compared with the normal control group(P<0.05),and there was no significant difference between spatial and tempora discrimination indexes on the 8^(th) and 15^(th) days after modeling.②Mifepristone before stress could significantly improve the spatial discrimination indexes of the foot-shock model(P<0.05),while propranolo could significantly improve temporal discrimination indexes(P<0.05).The combination of the two could significantly improve both the temporal and spatial discrimination indexes(P<0.05).CONCLUSION Foot-shock stress can damage both spatial and temporal pattern separation,while exogenous corticosterone injection stress can damage spatial pattern separation alone.Mifepristone can only improve the spatial pattern separation and propranolol can improve only the temporal pattern separation caused by foot-shock.The combination of the two drugs can significantly improve the temporal and spatial pattern separation deficit.