The Effect Of Paroxetine On PTSD Rats

Posttraumatic stress disorder (PTSD) is the development of long-lasting symptoms following the exposure to the life-threatening experience to which the immediate reaction is intense fear, helplessness, or honor. Resulting symptoms include re-experiencing of traumatic event, psychic numbing, increased arousal, and persistent avoidance. As the rapid increase of war, violence in society, disaster traffic accidents and natural disaster, PTSD has drawn great attention for its features that affect the clinical remedy such as high inception rate and morbidity rate, and bad curative effect, etc.The prevention and cure of PTSD is mainly focused on psychological counseling and pharmacotherapy. On the side of pharmacotherapy, antidepresants, especially SSRIS has caused extensive attention for its better effect to decrease the syndrome of PTSD and less adverse reaction than the other drugs. Among them, paroxetine and sertraline has been permitted by FDA to cure PTSD clinically. Whereas generally speaking the prevention and cure of PTSD has not developed well enough, the pharmacotherapy effectiveness of PTSD patients is very limited can only lessen partial syndrome. In this experiment, we chose SPS&S model with shock chamber, neutral test contextual , EPM , OF, MWM to assess the animal behaviour changes . To investigation when give paroxetine and possible preventive role , for clinical treatment and prevention of PTSD in choosing the drugs to provide new ideas.Objective:1. To establish a reasonable animal model of PTSD which seems to be high and reproducible2. To assess the animal behaviour changes of social conflict , fear response , anxiety-like behavior , horizontal distance , spatial learning and memory with paroxetine after stress3. To assess the animal behaviour changes of social conflict , fear response , anxiety-like behavior , horizontal distance , spatial learning and memory with paroxetine in stress before and afterMethods1. To tablished the SPS&S model Male Sprague–Dawley rats (8-week-old) were obtained from the animal center of the Fourth Military Medical University. The animals were housed three in a cage and maintained on a 12-h light/dark cycle (light on from 08:00– 20:00) with food and water freely available. After a 2-week acclimatization period, the animals were randomly assigned to one of the four groups: sham treatment (not subjected to SPS&S) followed by vehicle administration, the"Sham+Veh"group; SPS&S treatment followed by vehicle administration, the"SPS&S+Veh"group; sham treatment followed by paroxetine administration, the"Sham+PRX"group; and SPS&S treatment followed by paroxetine administration, the"SPS&S+PRX"group. Paroxetin was dissolved in water and applied via light -proof drinking bottles in doses of 0.1 mg/ml during the undisturbed period of 14 days after SPS&S. To observed conditional fear and sensitized fear at the 1,7,14day after SPS&S. The 15th day do EPM and OF test. To observe rats of which activities and spatial learning and memory capacity by Morris water maze in the 16th day.2. 40 adult male SD rats were chose randomly as Sham+Veh, Sham+PRX , SPS&S+Veh, SPS&S+PRX(0.1mg/ml), SPS&S+PRX(0.2mg/ml) in each group.Paroxetin was dissolved in water and applied during the undisturbed period of 14 days after SPS&S. Control animals received tap water. To observed conditional fear and sensitized fear at the 1,7,14day after SPS&S. The 15th day do EPM and OF test. To observe rats of which activities and spatial learning and memory capacity by Morris water maze in the 16th day.3. The animals were randomly assigned to one of the three groups: sham treatment : SPS&S+Veh, SPS&S+PRX, PRX+SPS&S, 12 rats were each group.Paroxetin was dissolved in water, The observation index and time management is the same as part 2 .RESULT1. The effect of fear response, anxiety-like behavior and horizontal distance after SPS&SCompare to Sham+Veh group, Conditioned fear persisted and sensitized fear increased with ongoing incubation time after SPS&S. SPS&S increased conditioned fear response and high alert. Shocked groups with different incubation times did not differ in conditioned contextual fear. Sensitized freezing to the neutral tone also increased as a function of incubation time. Compare to Sham+Veh group, The anxiety-like behavior and spatial learning and memory were increased with ongoing incubation time after SPS&S. The rats in SPS&S were representation significant the anxiety-like behavior and spatial learning and memory.2. The impact of paroxetine on the behavior, spatial learning and memory after stressCompare to SPS&S group, SPS&S+PRX decreased conditined fear response and Sensitized freezing . The percentage of open arm entries and percentage of time spent in the open arms in the SPS&S + PRX group was higher than that in the SPS&S+Veh group (p<0.05) . There was no significant difference between the SPS&S+PRX and Sham+Veh groups . The performance of learning and memory ability was improved in the SPS&S+PRX group .3. The impact of paroxetine on the behavior, spatial learning and memory after or before stress.Compare to SPS&S group, SPS&S+PRX or PRX+SPS&S decreased conditined fear response and Sensitized freezing. Post hoc analysis revealed that the percentage of open arm entries and percentage of time spent in the open arms in the SPS&S+PRX group or PRX+ SPS&S was higher than that in the SPS&S+Veh group (p<0.05). There was no significant difference between the SPS&S+PRX or PRX+SPS&S groups . SPS&S+PRX group was improved the learning and memory ability of rats after or before SPS&S .Conclusion1. Both increased conditioned fear response and high alert can be observed after SPS&S. SPS&S make these responses prominent .2. Compare to SPS&S group, SPS&S+PRX decreased conditined fear response and Sensitized freezing. SPS&S increase rats's the anxiety-like behavior and impair the spatial learning and memory capacity. Both the SPS&S and chronic paroxetine intervention had no effect on the spontaneous locomotor activity . 3. Compare to SPS&S group, SPS&S+PRX or PRX+SPS&S groups had a prominent decreased conditined fear response and sensitized freezing. The anxiety-like behavior was decreased and spatial learning and memory capacity were improved in the group of via PRX. PRX+SPS&S or SPS&S+PRX groups decrease rats's the anxiety-like behavior and spatial learning and memory capacity. Both the SPS&S and chronic paroxetine intervention had no effect on the spontaneous locomotor activity .