胆囊收缩素-4致大鼠焦虑及其对海马区别孕烯醇酮的影响

CCK-4 Induces Anxiety in Rats and Affects the Level of Allopregnanolone in Hippocampus

目的建立和优化胆囊收缩素-4(CCK-4)致大鼠焦虑模型,并初步探讨该模型的作用机制。方法雄性SD大鼠随机分为空白对照组和CCK-4(5,10 mg/kg)处理组,分别予皮下注射生理盐水和不同剂量的CCK-4。15 min后依次监测各组大鼠在旷场试验(OFT)和高架十字迷宫(EPM)中的行为变化,结束后通过ELISA法检测大鼠血浆中皮质酮浓度和海马区别孕烯醇酮(AP)含量。结果与空白对照组比较,不同剂量的CCK-4均能显著降低大鼠在OFT中央区或EPM开臂区的路程比例和停留时间比例(P<0.01),而平均速度差别无统计学意义(P>0.05);CCK-4处理组大鼠血浆中皮质酮水平较空白对照组显著升高(P<0.01),其海马区中AP含量则显著降低(P<0.01)。结论CCK-4能有效建立大鼠焦虑模型,其作用机制可能与大脑海马区AP含量下降有关。

Objective The animal model of anxiety by cholecystokinin-4(CCK-4)was developed and optimized and its mechanism was preliminarily explored.Methods Male SD rats were randomly divided into the control group,and 5 and 10 mg/kg dose of CCK-4 treatment groups(n=8).The rats were subcutaneously injected with saline or different doses of CCK-4,respectively.15 minutes later,the behaviors of animals were observ and recorded in open-field test(OFT)and elevated-plus maze(EMP)test,subsequently.After that,the levels of plasma corticosterone and the contents of allopregnanolone in rat hippocampus were measured by ELISA assays.Results Compared to control group,the treatments by both doses of CCK-4 significantly reduced the percentages of distance travel and persistent time spent in the center zone of OFT and the open arms of EMP,respectively(P<0.01),and both average velocities in OFT and EPM were not significantly altered(P>0.05).The levels of plasma corticosterone in CCK-4-treated rats were increased(P<0.01),while the concentrations of allopregnanolone in the hippocampus of anxious rats were decreased compared to the control group(P<0.01).Conclusion The animal model of anxiety induced by CCK-4 is effectively developed,the mechanism of which may be related to the reduction of allopregnanolone in hippocampus.