阿戈美拉汀对创伤后应激障碍SD大鼠行为表现的影响

Effect of Agomelatine on behavioral manifestations of rats with post-traumatic stress disorder

目的探究阿戈美拉汀对创伤后应激障碍(PTSD)SD大鼠行为表现的影响。方法将32只SD雄性大鼠随机分为空白对照组(不给药,不应激)、单纯应激组(不给药,应激)、药物组(给药,应激)及单纯药物组(给药,不应激)4组,每组8只。药物组和单纯药物组在应激后12 h内通过灌胃给予阿戈美拉汀2.6 mg∕(kg·d);空白对照组和单纯应激组通过灌胃给予等量生理盐水,共2周。单纯应激组和药物组给予大鼠单次延长结合足底电击应激刺激。第14天在电击箱中检测大鼠的条件性恐惧反应;第15天给予旷场实验,观察其焦虑状态;第16~21天行Morris水迷宫实验,测试其定位航行力和空间探索力。结果应激后大鼠在电击箱中呆滞时间延长;在旷场实验中穿格和站立次数减少;在Morris水迷宫实验中上台时间延长,穿越平台次数减少。相比单纯应激组,应激后早期给予阿戈美拉汀干预,大鼠呆滞行为、焦虑状态及其在Morris水迷宫中的表现均改善(P <0.05)。结论应激后大鼠警觉性和焦虑性增强,学习记忆功能减退。应激后早期给予阿戈美拉汀干预,能有效减少应激后PTSD模型大鼠恐惧、焦虑表现,并对大鼠的学习记忆能力减退有预防作用。

Objective To investigate the effect of Agomelatine on behavioral manifestations of rats with posttraumatic stress disorder(PTSD).Methods Thirty-two male SD rats were randomly divided into a control group(no drug,no stress,n=8),an SPS﹠S group(no drug,single prolonged stress﹠foot shock stress,n=8),a drug group(drug and stress,n=8)and a single drug group(drug,no stress,n=8).The rats of the drug group and the single drug group were administrated with Agomelatine in a dosage of 2.6 mg/(kg·d)by gavage within 12 h after stress for 2 w,while the control group and the SPS﹠S group were administrated with the same dose of saline for 2 w.After that the rats in the SPS﹠S group and the drug group were stimulated with SPS﹠S,the conditioned fear response was observed on the 14th d in the electric shock box.On the 15th d the open-field test was conducted in each group to observe the anxiety behaviors,while from the 16th d to the 21st d,the Morris water maze test was done to observe the navigation capability and the space exploration ability of the rats.Results After SPS﹠S stress,the retention time of the rats in the electric shock box was significantly prolonged while the crossing score and rearing score of the rats decreased significantly in the open-field test,and the Morris water maze test also indicated the escape latency period of the rats increased while the number of crossing platform decreased.Furthermore,compared with the SPS﹠S group,early intervention of Agomelatine after the stress obviously ameliorated sluggish behavior,anxiety state and performance of the rats in the Morris water maze(P<0.05).Conclusions After stress,the alertness and anxiety of the rats are sharply increased while the learning and memory functions obviously decrease.However,early intervention of Agomelatine after stress could significantly reduce the fear and anxiety-like behaviors of the rats with PTSD and can also prevent the loss of learning and memory functions in rats.