Study On The Prevention Of Post-traumatic Stress Disorder With Citalopram

Post-traumatic stress disorder(PTSD) refers to the delayed and long-lasting mental disorder following the exposure to the life-threatening experience(such as war,earthquake,danger,cruel torture or rape,etc).The major clinical manifestations of PTSD include re-experiencing of traumatic event,persistent high alertness,persistent avoidance and selective amnesia of the traumatic experience.Lots of stress-induced mental disorders,especially PTSD,emerge in modern war,which seriously influence the recurrence of the soldiers and thus aggravate the social burden.So the prevention and cure,especially prevention, become a significant topic to our military medical research.Selective serotonin reuptake inhibitors(SSRI) is considered with the best therapeutic effect and security,and thus usually used as the first consideration in the treatment of PTSD.As a kind of SSRI,citalopram has the best inhibitory effect and high selectivity on serotonin reuptake.Even though the total effect is similar to other SSRI,the curative effect of citalopram emerges faster.Drugs are used to the treatment of the PTSD,but in our research,basing on the rat PTSD model,with Open Field test(OF),Elevated Plus Maze(EPM),and Morris Water Maze(MWM) to clarify whether it is possible to reduce the occurrence or improve the symptoms of PTSD pretreatment or administration immediately after PTSD.And it may offer a new strategy for the prevention of PTSD.Objectives1.To make a reasonable animal model of PTSD with high similarity and good reproducibility.2.To clarify whether it is possible to reduce the occurrence or improve the symptoms of PTSD pretreatment or administration immediately after PTSD.Methods1.Establishment of the PTSD model:single prolonged stress and foot shock (SPS&S)The experiment was divided into 3 parts for excluding the influence of repeated stress to the observation index.Male adult Sprague-Dawley(SD) rats in each experiment were randomly divided into 2 groups:model group (SPS&S:restraint 2h,forced swimming test 20 min,rest for 15 min,loss of consciousness by etherization,foot shock after consciousness recovery),sham group.Control group animals(without SPS&S).The protocol is as follow:Part 1:to observe conditioned fear,sensitive fear and agitation behaviors at the 1^st day after SPS&S.Part 2:to observe conditioned fear,sensitive fear response and agitation behaviors at the 7^th after SPS&S.Part 3:to observe agitation behaviors,conditioned fear,sensitive fear response and agitation behaviors at the 14^th day after SPS&S.EPM and OF test.were observated To observe rats of which activities and spatial learning and memory capacity by Morris water maze from 16^th to 21^st day. 2.The effect of Citalopram on rat's behaviors,spatial learning and memory after or before stress.Male Sprague-Dawley(SD) were divided randomly into three groups: mode group(SPS&S),SPS&S+CIT,CIT+SPS&S.The protocal is as follow:â‘ model group:all animals were undisturbed period for 14 days,and then to make animal model.The agitation behaviors were observed at the 1^st,7^th day after SPS&S.The agitation behaviors,conditioned fear and sensitive fear response were observed at the 14^th day after SPS&S.The 15^th day do EPM and OF test.The navigation test was observed from the 16st to 20^th in the Morris water maze.The probe test was observed at the 21^st day.â‘¡CIT+SPS&S group: citalopram were dissolved in water and applied during the undisturbed period of 14 d;then we begin to make animal model.The observation index was the same as model group.â‘¢SPS&S+CIT group:all animals were undisturbed period for 14 days,then after SPS&S treatment,followed by citalopram(20 mg/kg) administration for 14 days.The observation index was the same as model group.Results1.The effect of rat's conditioned fear,sensitive fear response,agitation behaviors,horizontal distance,anxiety-like behavior,learning and memory ability after SPS&S.Compared to the Control group,the model group rat's freezing time was increased.SPS&S increased rat's conditioned fear,sensitized fear response and high alert;whether it the percentage of open arm entries or percentage of time spend in the open arms decreased significantly in the model group.Two groups rat's horizontal distance were no significant different in the OF test.The escaped latency increased compared to sham group,but percentage of target quadrant and number of crossing the platform decreased significantly in model group's.3.The effect of rat's conditioned fear,sensitive fear response,agitation behaviors,horizontal distance,anxiety-like behavior,learning and memory ability before and after SPS&S with citalopram.CIT+SPS&S and SPS&S+CIT compared to model group,CIT+SPS&S treatment didn't affect the conditioned fear,sensitized fear response,however, SPS&S+CIT didn't affect the sensitized fear response,but decreased the conditioned fear response.CIT+SPS&S and SPS&S+CIT compared to model group,the rat's agitation behaviors decreased significantly in two groups,however, CIT+SPS&S group reduced more significantly.CIT+SPS&S and SPS&S+CIT compared to model group,whether the percentage of open arm entries or percentage of time spent in the open arms increased in SPS&S+CIT group,but CIT+SPS&S group compared to model group no significant different.Citalopram intervention had no effect on the spontaneous locomotor activity.Compared to model group,two groups decreased rat's escaped latency,but SPS&S+CIT group more significant.It was insignificant different the percentage of target quadrant and number of crossing the platform in CIT+SPS&S group,however,there are two observation index increased significantly in SPS&S+CIT.Conclusion1.Conditioned fear,sensitive fear response,agitation behaviors,anxiety-like behavior increased significantly,learning and memory ability were injury after SPS&S. 2.The SPS&S+CIT group can revered all the behaviors of the above description, escaped for sensitive fear response.The CIT+SPS&S and SPS&S+CIT group compared with model group,the CIT+SPS&S and SPS&S+CIT group all can revered SPS&S induced spatial learning ability injury,but the SPS&S+CIT group more significant.So before or after post traumatic events early with citalopram may be to prevent or reduce the subsequent symptoms of PTSD.