The Experimental Study Of Drug In The Prevention Of Post-traumatic Stress Disorder In Early Time After Sps&s Stress

According to the DSM-III, PTSD was determined by the "development of characteristic symptoms of include reexperience, hyperarousal, avoidance and numbing following a psychiatrically traumatic event. Because the PTSD expesss usually the chronic progress and symptoms and very heavey incidence, thus the PTSD clinical therapy is very difficult, some body has PTSD in his life.Nowaday, the PTSD therapy included the pharmacological face. The important drug had treatment effect on PTSD has Selective Serotonin Reuptake Inhibitors (SSRIs), and has else antidepressants, typical and atypical antipsychotics etc. The research of the about PTSD pharmacotherapy has now no less in the world, but the research of the preventive PTSD has only a few, thus the study of the medicine prevention PTSD have very important sense in the world..The SPS&S animal model was used in our current experiment, the animal fear, anxiety activeness was evaluated in the Elevated plus Maze (EPM), Open-Field Test, and shock box etc, and the animal learning and memory ability was tested in the Morris Water Maze (MWM). In early after SPS&S stress, the rats was preventive administered the different category and dose drugs (Benzodiazepines Alprazolam, Novel Antidepressants Mirtazapine, Antiepileptic Carbamazepine, TCAs imipramine,β1adrenoreceptor blocade Metoprolol, Phenothiazine atypical Antipsychotics haloperidol). The fear, anxiety, and learning and memory were measured in rat. In our experiment, we screening drugs has the preventive effect on the PTSD and evaluating the best time of the persistence administer drug to provide the scientific reference for clinical medication and prevention of PTSD.Objectives:1. The rat was early administered drugs of the different category and dose which has the precaution effect on the conditioned fear, anxiety, learning and memory of the PTSD rats after SPS&S stress. We are screening the active drugs which can prevent PTSD in our experiment.2. To evaluate the active drug dose which can prevent PTSD and the shortest persistence time of the effect of the Mirtazapine and imipramine on PTSD rats when drugs was administered early after SPS&S stressing?Methods:1. The PTSD animal model-SPS&S model was established in this experimentMale Sprague–Dawley rats(8-week-old) were obtained from the Animal Center of the Fourth Military Medical University and housed four to a cage, maintained on a 12-h light/dark cycle (light on from 08:00 to 20:00), and fed and watered ad libitum. After a 2-week acclimatization period, the animals were randomly assigned to one of the following groups: (1) SPS&S group (2) control group (not subjected to SPS&S). SPS&S rats was stressed follow by: Rats were immobilized for 2 h, followed immediately with a 20-min forced swim conducted in a clear acrylic cylindrical tank (24 cm diameter, 50 cm height, 24 ?C water temperature) filled approximately two-thirds with water. After recuperating for 15min, rats were placed into the shock chamber and anesthetized with diethyl ether. After 30-min recovery, stressed rats received the electric foot shock within the shock chamber via the metal grid. After undisturbed feeding for 2 weeks in cage, the conditioned fear respond of rats was tested on the fourteenth day in shock box, the exploratory behavior and anxiety of rats was tested on fifteenth day in the open field and EPM, the learning and memory of rats was measured on from sixteenth to twenty-one day in MWM, to evaluate availability of the SPS&S animal model.2. The ways of the early administering drugs after SPS&S stress.Male Sprague–Dawley rats(8-week-old) were randomly assigned to one of the following groups: control group (not subjected to SPS&S), SPS&S group, single using drug group (only using at midst-dose dru and not subjected to SPS&S), after subjected to SPS&S low dose drug group, midst-dose drug group, marco-dose drug group, every group has eight rats. The rats were stressed follow up stress model preparative method, and were free fed with water that alprazolam(0.06 mg/kg/d,0.125 mg/kg/d), mitrazapine(0.375 mg/kg/d, 0.75 mg/kg/d, 1.5 mg/kg/d), carbamazepine(9.75 mg/kg/d, 19.5 mg/kg/d, 39 mg/ kg/d), imipramine(1.95 mg/kg/d, 3.9 mg/kg/d, 7.8 mg/kg/d), metoprolol(1.56 mg/kg/d, 3.125 mg/kg/d, 6.25 mg/kg/d), aloperidin(0.013 mg/kg/d, 0.025 mg/ kg/d, 0.05 mg/kg/d) were dissolved for 14 d, the conditioned fear respond of rats was tested on the fourteenth day in shock box, the exploratory behavior and anxiety of rats was tested on fifteenth day in the open field and EPM, the learning and memory of rats was measured on from sixteenth to twenty-one day in MWM. 3. The rat was administered Mirtazapine and imipramine for 3 and 7 days has influence on the Capability and learning and memory ability of the rats in early after SPS&S stress.Male Sprague–Dawley rats(8-week-old) were randomly assigned to one of the following groups: control group (not subjected to SPS&S) , SPS&S group, single using drug group (only using drug for 7d and not subjected to SPS&S), mitrazapine 3 d group (after subjected to SPS&S, using mitrazapine 0.75 mg/kg/d with 3 day), mitrazapine 7 d group (after subjected to SPS&S,using mitrazapine 0.75 mg/kg/d with 7 day), imipramine 3 d group (after subjected to SPS&S, using imipramine 3.9 mg/kg/d with 3 day), imipramine 7 d group (after subjected to SPS&S,using imipramine 3.9 mg/kg/d with 7 day), The rats were stressed follow up stress model preparative method, and were free fed with water that mitrazapine 0.75 mg/kg/d and imipramine 3.9 mg/kg/d were dissolved for 3d,7d, the exploratory behavior of rats was tested on the third day,seventh day in the open field, and the anxiety of rats was tested on fourth day,eighth day in the EPM, the learning and memory of rats was measured on from fifth to tenth day and from ninth to fourteenth in MWM.Results:1. After SPS&S stress, SPS&S stress has impact to the conditioned fear, anxiety and exploratory conduct and cognition of the rats.The ability of learning and memory of the rats after SPS&S stress has significant decrease compared with control group in the MWM (P <0.05), such as: the target quadrant time of the rats was delay and the number of crossing board of the rats decreases.The percentage of the open-arm into the maze and the percentage of the open arm pause of the rats after SPS&S stress has significant decrease compared with control group in the EPM (P <0.05).The freezing time of rats after SPS&S stress has obviously increase compared with control group in the shock box (P <0.05).The level active distance of rats after SPS&S stress has obviously decrease compared with control group in the open field (P <0.05).2. The early administering different category and dose drugs with 14 days has influence on the Capability and learning and memory ability of the rats after SPS&S stress.The ability of learning and memory of the drug group rats after SPS&S stress has significant increase compared with control group in the MWM (P <0.05), such as: the number of crossing board of the rats increase.The percentage of the open arm pause of the drug group rats after SPS&S stress, has significant increase compared with control group in the EPM (P <0.05).The freezing time of the drug group rats after SPS&S stress has obviously decrease compared with control group in the shock box (P <0.05).The level active distance of the drug group rats after SPS&S stress has obviously increase compared with control group in the open field (P <0.05).3. The early continued administering Mirtazapine and imipramine for 3 and 7 days has influence on the Capability and learning and memory ability of the rats after SPS&S stress.The ability of learning and memory of the imipramine 7 d group rats after SPS&S stress has significant increase compared with control group in the MWM (P <0.05), such as: the number of crossing board of the rats increase.The percentage of the open arm pause of the Mirtazapine 7 d group and imipramine 3 d,7 d group rats after SPS&S stress has significant increase compared with control group in the EPM (P <0.05).The level actived distance of the drug group rats after SPS&S stress has obviously increase compared with control group in the open field (P <0.05).Conclusion:1. We determined that Alprazolam,Mirtazapine,Carbamazepine,imipramine,Metoprolol and haloperidol has the preventive effect on the PTSD rats, but Mirtazapine and imipramine has be better effect than the drugs else.2. The shortest persistence time of the early using Mirtazapine and imipramine intervention PTSD is three days. The continued administer imipramine with 7 day can ameliorate decrease of learning and memory ability of rats caused by stress.