Mk-801诱导的精神分裂症选择性记忆缺陷模型的研究

发布时间：2018-06-29 05:29

本文选题：精神分裂症 + MK-801　；参考：《中南大学》2012年硕士论文

【摘要】：目的：以NMDA受体拮抗剂MK-801为工具药,予成年期SD大鼠急性注射中低剂量的MK-801药物,制作精神分裂症的动物模型,通过自发活动、前脉冲抑制实验和新奇物体识别实验来探讨不同剂量的MK-801诱导的行为学变化,寻找适宜的能够塑造不同认知缺陷模型的可靠、适宜的药物剂量。研究方法： 1.204只成年健康雄性SD大鼠随机分为实验组和对照组。实验组大鼠分别给予MK-801低剂量0.01mg/kg,0.03mg/kg和中剂量0.1mg/kg、0.3mg/kg腹腔注射,对照组予生理盐水腹腔注射,分别独自进行旷场实验测试,惊跳反射的前脉冲抑制测试,新奇物体识别实验。研究结果： 1.MK-801急性注射对自发活动影响：在中低剂量时可表现为自发活动增加和轻度共济失调,给药后自发活动明显增加,表现出剂量依赖性的行为学效应。0.3mg/kg组在50min-90min均表现出显著性差异(P0.05),余处理组自发活动有增多的趋势,但与对照组相比,无统计学差异。 2.MK-801急性注射对前脉冲抑制实验的影响： (1).0.1mg/kg剂量组和0.3mg/kg剂量组与盐水对照组均有统计学差异,且0.1mg/kg组惊跳反射反应振幅最高。MK-801在不同剂量范围内明显抑制了PPI的水平(P0.001),不同的前脉冲预刺激强度也对PPI产生了影响(P0.001)。PPI表现出MK-801剂量依赖式的变化效应。MK-801的剂量愈大,PPI值愈低,说明对PPI的损害愈大；前脉冲预刺激的强度愈大,对惊跳反射抑制的程度愈深。 3. MK-801急性注射对新奇物体识别实验的影响：新物体探索时间均超过了50%,明显的多于探索旧物体时间。不同剂量MK-801与对照组分辨指数的比较,存在显著差异(P0.05)。盐水对照组大鼠的物体识别分辨指数最高,表现出良好的识别分辨能力；0.03mg/kg剂量组和0.1mg/kg剂量组分辨指数显著低于盐水对照组(其P值分别为0.002、0.025),MK-8-1明显的损害了大鼠的识别记忆能力。结论： 1.成年期SD大鼠急性腹腔注射MK-801可以引起自发活动的增加,在中低剂量范围呈现剂量依赖性的行为学效应,在0.3mg/kg剂量能够较好地模拟SZ的阳性症状。 2.成年期SD大鼠急性腹腔注射MK-801可以引起PPI不同程度的损害,在中低剂量范围整体表现出剂量依赖性的变化趋势,0.1mg/kg剂量是MK-801诱导的SZ动物模型感觉运动门控缺陷一个相对适宜的剂量。 3.成年期SD大鼠急性腹腔注射MK-801可引起视觉情景记忆的损害,模拟SZ的认知损害,0.03mg/kg剂量是塑造这一模型相对理想、单纯的适宜剂量。该模型是动物实验一个极为有用的工具,将有助于我们研究有关学习和记忆的神经生物机制和研发新型促认知精神药物。
[Abstract]:Objective: to establish an animal model of schizophrenia with MK-801, a NMDA receptor antagonist, by acute injection of MK-801 into adult Sprague-Dawley rats. Pre-pulse inhibition and novel object recognition experiments were used to investigate the behavioral changes induced by MK-801 at different doses, and to find a reliable and suitable drug dose that could model different cognitive defect models. Methods: 1.204 adult male SD rats were randomly divided into experimental group and control group. Rats in the experimental group were given intraperitoneal injection of MK-801 low dose 0.01mg / kg 0.03mg / kg and middle dose 0.1 mg / kg 0.3mg / kg, respectively. The control group was injected intraperitoneally with normal saline. The rats in the control group were given open field test alone, prepulse inhibition test of shock reflex and novel object recognition experiment. Results: 1. The effect of acute injection of MK-801 on spontaneous activity: at low and low doses, it showed increased spontaneous activity and mild ataxia, and increased spontaneous activity after administration of MK-801. The behavioral effect of 0.3mg / kg in dose-dependent manner showed significant difference in 50min-90min (P0.05). The spontaneous activity of the remaining treatment group increased, but compared with the control group. 2. The effect of acute injection of MK-801 on the prepulse inhibition test: (1) there were significant differences between the 0.1 mg / kg dose group and the 0.3mg/kg dose group and the saline control group. In 0.1mg/kg group, the amplitude of shock reflex response was the highest. MK-801 significantly inhibited the level of PPI in different dose range (P0.001). Different prestimulation intensity also affected PPI (P0.001). PPI showed a dose-dependent effect of MK-801. The higher the dose of MK-801, the lower the PPI value. It is concluded that the greater the damage to PPI and the greater the intensity of prepulse prestimulation, the greater the degree of inhibition of shock reflex. The effect of acute injection of MK-801 on novel object recognition experiments: the exploration time of new objects exceeded 50 obviously more than that of old objects. There was significant difference in resolution index between MK-801 and control group (P0.05). In the saline control group, the object recognition resolution index was the highest and showed good recognition and resolution ability. The resolution index of 0.03mg/kg group and 0.1mg/kg group was significantly lower than that of saline control group (P = 0.002 0. 025) MK-8-1 significantly impaired the recognition and memory ability of rats. Conclusion: 1. Acute intraperitoneal injection of MK-801 in adult Sprague-Dawley (SD) rats could induce an increase in spontaneous activity, showing a dose dependent behavioral effect in the low and middle dose range. The positive symptoms of SZ could be well simulated at the dose of 0.3mg/kg. 2. Acute intraperitoneal injection of MK-801 in adult Sprague-Dawley rats caused different degrees of PPI damage. The dose of 0.1 mg / kg is a relatively suitable dose for sensorimotor gating defect induced by MK-801 in SZ animal model. Acute intraperitoneal injection of MK-801 in adult Sprague-Dawley rats resulted in the impairment of visual situational memory. The dose of 0.03 mg / kg simulated SZ cognitive impairment was a relatively ideal and simple appropriate dose to model the model. This model is an extremely useful tool for animal experiments, which will help us to study the neurobiological mechanisms of learning and memory and to develop new cognitive psychoactive drugs.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.3

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