帕罗西汀和西酞普兰对急性应激障碍和创伤后应激障碍的不同预防作用

利用急性强迫游泳(FST)以及单次延长的应激(single-prolonged stress,SPS)模型分别模拟急性应激障碍(ASD)和创伤后应激障碍(PTSD),利用FST中不动时间作为应激障碍指标,评价两种5-HT再摄取抑制剂(SSRIs)帕罗西汀或西酞普兰对ASD和PTSD可能的预防作用。大鼠经过或不经过SPS处理(包括2h束缚,20min FST,休息15min后乙醚麻醉至意识丧失)后,每天通过饮用水给予不同剂量的帕罗西汀(20或40mg/kg)、西酞普兰(20或30mg/kg)或者正常进食水,连续14d后进行20minFST,计算该期限内每5min的不动时间,进行统计学分析,观察帕罗西汀和西酞普兰对动物行为的影响。SPS14d后大鼠的不动时间显著延长(0~5min:P<0.05,vs正常大鼠;5~10min:P<0.01,vs正常大鼠)。连续给予14d20mg/kg帕罗西汀显著缩短动物的不动时间(0~5、5~10和10~15min:P<0.05,vsSPS大鼠)。40mg/kg帕罗西汀以及20/30mg/kg西酞普兰显著缩短0~5min内的不动时间(P<0.05,vsSPS大鼠),但对其余时间点的不动时间没有影响(P>0.05,vsSPS大鼠),相反,40mg/kg帕罗西汀预处理还导致动物在15~20min内的不动时间显著延长。正常大鼠经过14d帕罗西汀或西酞普兰预处理后,0~5和5~10min的不动时间与饮用水对照相比没有显著差异。我们的实验结果提示较低临床剂量帕罗西汀和西酞普兰都可以用于预防ASD,较低剂量帕罗西汀预防PTSD的效果明显好于西酞普兰,同时我们的实验结果还提示对于ASD或PTSD的预防来说,增大抗抑郁药物的剂量,并不一定能取得期望的增加的疗效。

Different preventive effects of paroxetine and citalopram for acute or post-traumatic stress disorder

To observe the effect of two selective serotonin reuptake inhibitors(SSRIs),paroxetine and citalopram,on the acute forced swim test(FST)and single-prolonged stress(SPS)models which mimic acute stress disorder(ASD)and post traumatic stress disorders(PTSD).Rats receiving SPS(2 h restraint+20 min FST+anaesthesized to lose consciousness with ethylether)or not were given paroxetine(20 or 40 mg/kg·d,via feeding water),citalopram(20 or 30 mg/kg·d,via feeding water)or tap water for 14 days.FST behaviors were observed on the 14th day and immobilization time(IT)were ploted on a 5 min pin and compared for different treatments.Fourteen days after SPS,IT in FST was significantly increased in SPS group,(0-5 min,P<0.05,vs control;5-10 min,P<0.05,vs control).Fourteen days pretreatment with 20 mg/kg·d of paroxetine significantly reduced the IT of SPS rats(P<0.05,vs SPS;for 0-5,5-10 and 10-15 min intervals).While 40mg/kg·d of paroxetine and 20-30mg/kg·d of citalopram significantly decreased the IT of SPS rats at only the 0-5 min interval(P<0.05,vs SPS)but had no effect on the IT at other intervals(P>0.05,vs SPS).On the contrary,high dose of paroxetine [40 mg/kg·d] induced a significantly increased IT(P<0.05,vs SPS)during the 5-20 min interval.Control rats received 14 d paroxetine or citalopram treatment had similar IT to that of control rats receiving only tap water.Our data suggested that lower dose of paroxetine and citalopram can be effective in preveenting ASD,while as to the case for PTSD,lower lose of paroxetine has a better preventive effect that citalopram.Meanwhile,our data also suggested that increased the dose of SSRIs for PTSD may not produce the expected better effect.