The Experimental Study Of Fluoxetine In The Prevention Of Post-traumatic Stress Disorder

In recent years, Post Traumatic Stress Disorder (PTSD) is a kind of common clinical mental disorder , which is closely related to the stressful events, and it was commonly occurs in the victims of traumatic events . also PTSD provoked more and more attention for it's complex of symptom, high prevalence and severe clinical outcomes . A higher incidence and worse outcomes in military personnel was found under the condition of combat .Whole how to prevent the PTSD effectively become a point of clinical and military psychiatry field.pharmacotherapy and psychotherapy are currently main effective clinical treatment for PTSD, although there are no one treatment can resolved the symptoms of PTSD patients completely。Many studies has showed Selective Serotonin Reuptake Inhibitors (SSRIs) was effective in treatment of PTSD ,and recommended as the first line drugs in treatment of PTSD by the WFSBP. But pharmacotherapy is used only after the PTSD symptoms have appeared which can just alleviate symptoms partly. There are few study reported that the doctors use medication prevention before the PTSD appears. In the experiments, many animal simulation models have been used, but they couldn't completely simulate the two kinds of reactions similar to clinical PTSD symptoms, including the increasing (high alertness) and the abating (avoiding and emotional numbing) under the stressful stimulus. Among the current PTSD animal models, single prolonged stress model (SPS) is widely used due to its better simulation of PTSD clinical manifestations and keeping the SPS stress symptoms for a long time. With the SPS model, we can observe the rats fear, anxiety, athletic ability and learning and memory ability through behavioral approaches, such as: the Elevated Plus Maze, EPM; Open-Field Test; Morris Water Maze (MWM) etc. In this paper, we begin with producing and preparing the model similar to clinical symptoms of post-traumatic stress disorder, discussing the feasibility of preventive selective serotonin reuptake inhibitors (SSRIs) Fluoxetine intervention before the PTSD symptoms have appeared in rats before or after the stress. This provides the scientific basis for clinical prevention of PTSD and medication.Objectives:1. establishment of proper animal models with steady repeatability and highly similarity to clinical PTSD symptoms.2. Evaluate the different influence to rats agitation behavior, fear response, anxiety behavior, motor ability, and learning and memory ability between Fluoxetine is used early and preventively before and after traumatic stress, to discuss the preventive effect of the early Fluoxetine intervention to PTSD animal models.Methods:1. The establishment of PTSD animal model---SPS model: The healthy adult male SD rats were randomly divided into two groups, the model group (SPS, n = 12), blank control group (Control, n = 12), then model group finished the single prolonged stress as showed as follow: The rats were bound for 2 hours, and then put in the water with the temperature between 23-25 degrees, at last forced to swim for 20 minutes in swimming pool. After that, they had a break of 15 minutes, and then they lost consciousness with aether anesthesia. The rats under anesthesia would be put in well-ventilated place until they woke up naturally, and then fed in the cage undisturbed for 14 days. On the 15th day after the stress, these rats are put in the open-field for researchers to observe their spontaneous activity and in the elevated plus-maze for researchers to observe the anxiety-like response. On the 16th day the researchers will test the rats'learning and memory ability in the MWM.2. The influence to the rats'behavior ability and place learning and memory ability when Fluoxetine intervention is given early after the stress.Experimental animals are randomly divided into six groups (n=8):control group (Control, Sham + VEH), and they don't have SPS and drug intervention; simple Fluo group (F, Sham + Fluoxetine 3 mg / kg), given drug without experience SPS; in model group (SPS, SPS + VEH), experience SPS without drug intervention; Fluoxetine intervention group 1 (F1, SPS + Fluoxetine 3 mg / kg), with SPS and drug intervention (3mg/kg Fluoxetine); Fluoxetine intervention Group 2 (F2, SPS + Fluoxetine 10 mg / kg), with SPS and drug intervention (10mg/kgFluo/d);Results:1. The impact to the rats'fear reaction, anxiety-like behavior and learning and memory ability after the SPS stress. After the SPS, in the open-field test: compared with the control group, there are significant difference s (P <0.05) showed in the level movement distance and the central place retention period in five minutes.After SPS, in the elevated plus-maze test: compared with the control group, there are significant difference s (P <0.05) showed in the percentage of the open-arm into the maze and the percentage of the open arm pause of the SPS rats.After SPS, in the Morris water maze test: in comparison with the control group, there are significant difference s (P <0.05) showed in the period of staying on board, the target quadrant time and the number of crossing board of the SPS rats.2. The influence to the rats'behavior ability and place learning and memory ability when Fluoxetine intervention is given early after the stress.In the open-field test: comparing with the simple stress group, the level movement distance and the central movement time of the rats in the post stress medication group increases remarkably in spite of the different dosage. Incontray, there are no different between F group and Control group.In the elevated plus-maze experiment: compared with the simple stress group, there are significant difference s (P <0.05) showed in the time of staying in the open arm and the number of entering the open arm of the rats in the post stress medication group in spite of the different dosage .In MWM experiment: compared with the simple stress group, there are significant difference s (P <0.01) showed in the orientation navigation test, the time of staying on board of the rats with medication treatment after stress decrease remarkably. And there exists no significant difference between the two medication group rats and the blank control group in the time of staying on board. On the contrary , In the dimensional exploration test, the percentage of staying at target quadrant time of the post stress rats with medication increase notably comparing with the rats in the simple stress group(P <0.05). There exists no significant difference in incubation period on board among the two medication group and the blank control group.Conclusion:1. With the SPS we can observe the rats'spatial cognition going down, the fear and anxiety rising, and the exploring activity being restrained and becoming dull. The above indexes have shown that after SPS the rats better simulate the symptoms of PTSD. It can be used as a ideal animal model for further studying in the pathogenesis and pharmacological mechanisms of the PTSD.2. Fluoxetine intervention can improve the response of the PTSD animal model to the stress. The improvements can be clearly seen in the increase of the level movement distance and the central movement time in the open-field test; the distinctive increase of the percentage of the open-arm and the percentage of the open-arm pause in the elevated plus-maze test; and also the shortened period of staying on board, the prolonged target quadrant time and the lager number of crossing board in the morris water maze test.