盐酸哌甲酯对自发性高血压大鼠行为及前额叶突触超微结构的影响

Effects of Methylphenidate on Behavior and Ultrastructures of Synapse in Prefrontal Cortex of Spontaneous Hypertension Rats

目的观察盐酸哌甲酯(MPH)对自发性高血压大鼠(SHR)行为及前额叶突触超微结构的影响,探讨注意缺陷多动障碍(ADHD)可能存在的发病机制。方法将22只ADHD动物模型SHR随机分为2组:MPH给药组(MPH组,n=11)和9g.L-1盐水对照组(SAL组,n=11),分别予MPH(2mg.kg-1)、9g.L-1盐水各1mL,2次.d-1,共14d。分别利用Làt迷宫、Morris水迷宫观察2组大鼠自发活动、非选择性注意力和学习记忆能力;完成行为学实验后,每组各随机抽取3只,利用电镜技术观察2组大鼠前额叶皮质突触超微结构。结果 1.Làt迷宫中,给药前MPH组水平活动、直立次数和斜搭次数与SAL组比较差异无统计学意义;给药14d后,MPH组水平活动、直立次数和斜搭次数较SAL组显著降低(Pa=0.00)。Morris水迷宫实验第1天,MPH组潜伏期和总路程与SAL组比较差异无统计学意义;第2天、第3天,MPH组潜伏期和总路程较SAL组显著降低(Pa=0.01,0.02)。2.电镜结果显示MPH组较SAL组突触数目增加,突触间隙增宽,突触后致密物厚度增加,差异有统计学意义(Pa=0.01,0.02,0.01);2组突触活性区长度比较差异无统计学意义。结论 MPH长期用药在改善SHR行为的同时可引起SHR前额叶突触超微结构的变化,提示突触超微结构的异常可能参与ADHD的发病。

Objective To investigate the effects of methylphenidate（MPH） on behavior and ultrastructures of synapse in prefrontal cortex（PFC） of spontaneous hypertension rats（SHR） and explore the pathogenesis of attention deficit hyperactive disorder（ADHD）.Methods Twenty-two SHR of animal models of ADHD were divided into 2 groups（11 rats in each group）：MPH group and saline（SAL） group,they were given MPH（2 mg.kg-1） or saline 1 mL,twice per day,for 14 days,respectively.The effects of MPH on locomotor activity,non-selective attention and learning and memory abilities of SHR were examined by Làt maze and Morris water maze,respectively.Then 3 rats were selected randomly from each group,and the effects of MPH on ultrastructures of synapse in PFC of SHR were examined by electron microscope.Results 1.In Làt maze,prior to the administration,there were no significant difference in the horizontal and vertical activities prior to the administration,or in the frequencies of leaning on the plastic wall between 2 groups.Following 14 days of repeated treatment,compared with SAL group,MPH group had significantly lower level performance both in horizontal and vertical activities compared with SAL group,as well as lower frequencies of leaning on the plastic wall（Pa=0.00）.Meanwhile,in Morris water maze,there were no significant difference in the latencies and the total distances between 2 groups on the first day,while the latencies and the total distances were significantly lower in MPH group than those in SAL group during the second day and the third day（Pa=0.01,0.02）.2.Electron microscopic photographs showed that the number of synapses was increased,and the width of synapses gap and the thickness of postsynaptic density became thickened in PFC of MPH group,compared with that in SAL group,and the differences were remarkably significant（Pa=0.01,0.02,0.01）,while the length of the synapses activity area was not remarkably different.Conclusions When the behaviors of SHR were improved with chronic administration of MPH,the number and some ultrastructures of synapse in PFC were also changed.Abnormal synaptic ultrastructures may be involved in the etiology and pathogenesis of ADHD.