喹硫平干预对PCP诱导的大鼠精神分裂症样行为及髓鞘异常的影响的研究
发布时间：2018-09-13 16:48
【摘要】：研究目的： 本研究的主要目的是探讨在新生期大鼠慢性给予苯环己哌啶（一种NMDA受体拮抗剂，英文名为Phencyclidine, PCP）处理后，大鼠能否在青春期表现出髓鞘的发育缺陷及类精神分裂症样行为，从而发展出一种新的可用于研究精神分裂症髓鞘/少突胶质细胞异常假说的动物模型。同时，本研究还选择了喹硫平这一对髓鞘损害有保护作用的非典型抗精神病药物，观察其对PCP诱导的精神分裂症样行为及髓鞘异常的影响，以进一步确立该模型的预测效度。 研究方法： 本研究中所有的实验均为动物实验，共分为两部分进行：第一部分为PCP干预后对大鼠的髓鞘变化及行为学异常的观察，第二部分则是探讨喹硫平能否逆转PCP诱导的精神分裂症样行为及髓鞘异常。 在第一部分，动物被随机分为两组：（1）生理盐水对照组，从出生后第2天起即给予实验动物（新生大鼠）连续14天的生理盐水颈部皮下注射，至出生后15天止，注射剂量为1ml/kg；（2）PCP干预组，从出生后第2天起即给予实验动物连续14天的PCP颈部皮下注射，PCP注射液浓度为1mg/ml，注射剂量为10mg/kg。 在第二部分，动物被随机分为四组：（1）生理盐水对照组，从出生后第2天起即给予实验动物每天2次、连续14天的生理盐水颈部皮下注射，至出生后第15天止，每天2次注射的间隔时间为30min。从出生后第16天至出生后第20天给予实验动物每天1次的生理盐水注射。生理盐水每次注射剂量均为1ml/kg；（2）PCP干预组，从出生后第2天起即给予实验动物连续14天的生理盐水和PCP分次颈部皮下注射，先注射生理盐水，后注射PCP，2次注射的间隔时间为30min。从出生后第16天至出生后第20天给予实验动物每天1次的生理盐水注射。PCP注射液浓度为1mg/ml，注射剂量为10mg/kg。生理盐水每次注射剂量均为1ml/kg。（3）喹硫平干预组，从出生后第2天起即给予实验动物连续14天的喹硫平和生理盐水分次颈部皮下注射，先注射喹硫平，后注射生理盐水，2次注射的间隔时间为30min。从出生后第16天至出生后第20天给予实验动物每天1次的喹硫平注射。喹硫平注射液浓度为1mg/ml，注射剂量为10mg/kg。生理盐水每次注射剂量均为1ml/kg。（4）喹硫平及PCP双干预组，从出生后第2天起即给予实验动物连续14天的喹硫平和PCP分次颈部皮下注射，先注射喹硫平，后注射PCP，2次注射的间隔时间为30min。从出生后第16天至出生后第20天给予实验动物每天1次的喹硫平注射。喹硫平及PCP的注射液浓度均为1mg/ml，注射剂量均为10mg/kg。 观察指标有两个方面，一是行为学观察：（1）自发活动测试，用来评定大鼠的自发活动增强现象；（2）PPI测试，用来评定大鼠的感觉运动门控功能损害程度。二是髓鞘发育情况的观察：运用免疫组织化学、Westernblot及电子显微镜等技术观察实验动物脑内PFC区的髓鞘发育变化情况。 结果：在实验的第一部分，给予新生期大鼠PCP干预后，我们发现在大鼠出生后第16天、第22天、第32天均可检测到大脑PFC区的髓鞘发育缺陷，主要表现为成熟少突胶质细胞数量的减少、髓鞘束分布范围的缩小以及MBP蛋白表达的降低，在出生后第32天还发现了白质的超微结构病理改变。同时，在出生后第30天和第31天进行的行为学检测发现这些大鼠可产生精神分裂症样行为。具体如下： 1.我们对大鼠出生后第16天的髓鞘发育情况进行了观察。首先，与生理盐水对照组相比，PCP组大鼠脑PFC区的成熟少突胶质细胞（GST-π阳性细胞）数目明显减少（P 0.05, t-test）；其次，在对照组大鼠脑切片的PFC区存在比较致密的由抗-MBP抗体免疫标记的髓鞘束，而在PCP组大鼠的相同区域却观察到了髓鞘束的分布范围的减少，对其光密度值进行的定量分析表明，与对照组相比，PCP组大鼠PFC区的髓鞘束密度明显降低（P 0.05, t-test）；最后，对实验大鼠的脑PFC区的MBP蛋白进行了Western Blot检测，对Western Blot条带的光密度进行的定量分析显示，与对照组相比，PCP组大鼠脑PFC区的MBP表达明显降低（P 0.05, t-test）。 2.我们对大鼠出生后第22天的髓鞘发育情况进行了观察。结果发现，与生理盐水对照组相比，PCP组大鼠脑PFC区的GST-π阳性细胞数目仍然明显减少（P 0.05, t-test），其髓鞘束密度明显降低（P 0.05, t-test），且其MBP的表达仍然显著低于对照组（P 0.05, t-test）。但与出生后第16天相比，对照组及PCP组大鼠脑PFC区的髓鞘束均显得更为致密，且覆盖范围更广，提示在此期间，髓鞘/少突胶质细胞正在迅速的发育。 3.我们对大鼠出生后第32天的髓鞘发育情况进行了观察。结果发现，，PCP组大鼠脑PFC区仅在MBP的表达上显著低于对照组（P 0.05, t-test），而GST-π阳性细胞数和髓鞘束密度与对照组相比无明显差异（P0.05）。这种结果的不一致可能是检测方法的灵敏度不同所导致的（Western Blot检测具有更高的灵敏度）。另外，电子显微镜观察显示，在PCP组的某些髓鞘部位可看到髓鞘层的局部降解以及致密的层间小体正在形成。 4.为了评估PCP干预造成的精神分裂症样行为，我们对出生后第30和第31天的大鼠进行了自发活动及PPI的检测。结果表明，与对照组相比，PCP干预组大鼠自发活动明显增多（P 0.05, t-test），且PCP干预对PPI产生了明显影响[F(1,34)=13.48, P=0.0008]，Post-hoc分析显示，与对照组相比，PCP组大鼠在PP8和PP16水平，其PPI(%)显著降低（P 0.05）。 在实验的第二部分，我们发现喹硫平在10mg/kg剂量下不能改善PCP引起的髓鞘发育缺陷，也不能改善与髓鞘异常相关的反映精神分裂症认知症状的PPI的损害，但能够缓解PCP引起的反映精神分裂症阳性症状的模型动物自发活动增多。具体如下： 1.我们对四组大鼠出生后第16天的髓鞘发育情况进行了观察。单因素方差分析显示，四组实验大鼠PFC区的GST-π阳性细胞数目存在明显差异[F(3,12)=5.493, P=0.0131]，髓鞘束分布范围存在明显差异[F(3,12)=30.93, P 0.0001]，且MBP的表达亦存在明显差异[F(3,12)=37.77, P 0.0001]。而Post-hoc分析显示，与对照组相比，PCP干预造成了GST-π阳性细胞数量的减少、髓鞘束的分布范围的减少以及MBP蛋白表达的减少，而在PCP注射前加用10mg/kg的喹硫平并不能逆转这些病理及生化变化（P 0.05）。 2.我们对四组大鼠出生后第32天的髓鞘发育情况进行了观察。单因素方差分析显示，四组实验大鼠脑PFC区仅在MBP的表达上存在显著差异[F(3,12)=23.30, P 0.0001]，而在GST-π阳性细胞数量[F(3,12)=0.6297, P=0.6097]及髓鞘束的分布范围[F(3,12)=0.3711, P=0.7754]上无统计学差异。Post-hoc分析显示，与对照组相比，PCP干预造成了MBP表达的下降，而在PCP注射前加用10mg/kg的喹硫平并不能逆转这种变化（P0.05）。 3.我们对出生后第30和第31天的大鼠进行了自发活动及PPI的检测。结果表明，四组大鼠间的自发活动存在明显差异[F(3,34)=3.625, P=0.0226]，PCP和/或QUE干预对PPI有显著影响[F(3,64)=8.235, P=0.0001]。与对照组相比，PCP干预组大鼠自发活动明显增多，PPI%显著下降，而在PCP注射前加用10mg/kg的喹硫平能够缓解PCP引起的模型动物自发活动增多，但不能逆转PPI的损害（P 0.05）。 结论： 在新生期大鼠慢性给予PCP处理后，大鼠在青春期会表现出髓鞘的发育缺陷以及类精神分裂症样行为，且两者间有一定的相关性，提示髓鞘异常在精神分裂症的病理发生中扮演着一定的作用，可将该模型用于研究精神分裂症的髓鞘/少突胶质细胞异常假说研究。同时，喹硫平在10mg/kg剂量下不能改善PCP引起的髓鞘发育缺陷，也不能改善与髓鞘异常相关的反映精神分裂症认知症状的PPI的损害，但能够缓解PCP引起的反映精神分裂症阳性症状的自发活动增多。
[Abstract]:Research purposes:
The aim of this study was to investigate whether chronic administration of phenylcycloperidine (PCP), a NMDA receptor antagonist, could induce developmental deficiency of myelin sheath and schizophrenic-like behavior during puberty in neonatal rats, thereby developing a new type of myelin sheath/oligospermia that can be used to study schizophrenia. At the same time, we selected quetiapine, an atypical antipsychotic drug with protective effect on myelin sheath damage, to observe its effect on schizophrenia-like behavior and myelin sheath abnormality induced by PCP, in order to further establish the predictive validity of the model.
Research methods:
All the experiments in this study are animal experiments, divided into two parts: the first part is the observation of myelin sheath changes and behavioral abnormalities in rats after PCP intervention, the second part is to explore whether quetiapine can reverse the PCP-induced schizophrenia-like behavior and myelin sheath abnormalities.
In the first part, the animals were randomly divided into two groups: (1) saline control group, from the second day after birth, the experimental animals (neonatal rats) were given saline subcutaneously for 14 consecutive days, until 15 days after birth, the dose of injection was 1ml/kg; (2) PCP intervention group, from the second day after birth, the experimental animals were given PCP neck for 14 consecutive days. Subcutaneous injection, PCP injection concentration of 1mg/ml, injection volume of 10mg/kg.
In the second part, the animals were randomly divided into four groups: (1) saline control group, the experimental animals were given saline subcutaneously twice daily for 14 days from the second day after birth, and the interval between the two injections was 30 minutes from the 15th day after birth. Each injection dose of saline was 1 ml/kg; (2) PCP intervention group, from the second day after birth, was given 14 consecutive days of saline and PCP subcutaneous injection of cervical, first injection of saline, then injection of PCP, the interval between the two injections was 30 minutes. The experimental animals were injected with normal saline once a day. The concentration of PCP injection was 1 mg/ml and the dosage of PCP injection was 10 mg/kg. The dosage of physiological saline was 1 ml/kg per injection. The interval between the two injections was 30 minutes. From the 16th day after birth to the 20th day after birth, the experimental animals were given quetiapine injection once a day. The concentration of quetiapine injection was 1 mg/ml and the dosage of quetiapine injection was 10 mg/kg. The animals were subcutaneously injected with quetiapine and PCP for 14 consecutive days. The interval between the two injections was 30 minutes. From the 16th day to the 20th day after birth, the animals were injected with quetiapine once a day. The concentrations of quetiapine and PCP injection were 1 mg/ml, and the doses were 10 mg/kg.
There are two aspects to observe the indexes, one is behavioral observation: (1) spontaneous activity test, used to assess the phenomenon of spontaneous activity enhancement in rats; (2) PPI test, used to assess the degree of sensorimotor gating function damage in rats. The other is the observation of myelin sheath development: using immunohistochemistry, Western blot and electron microscopy technology observation. The development of myelin sheath in PFC region of experimental animals.
RESULTS: In the first part of the experiment, after PCP intervention in neonatal rats, we found that myelin sheath defects were detected on the 16th, 22nd and 32nd day after birth in rats, mainly manifested by the decrease of the number of mature oligodendrocytes, the narrowing of myelin bundle distribution and the decrease of MBP protein expression. Ultrastructural and pathological changes of white matter were also observed on the 32nd day after birth. Behavioral tests on the 30th and 31st days after birth showed that these rats had schizophrenic behavior.
1. We observed the myelin sheath development on the 16th day after birth in rats. Firstly, compared with the normal saline control group, the number of mature oligodendrocytes (GST-pi positive cells) in the PFC region of the rat brain in the PCP group was significantly decreased (P 0.05, t-test); secondly, there was a relatively dense immunization from anti-MBP antibody in the PFC region of the rat brain slices in the control group. Compared with the control group, the density of myelin bundles in the PFC region of the rats in the PCP group decreased significantly (P 0.05, t-test), and the MBP protein in the PFC region of the brain of the experimental rats was detected by Western blot. Blot assay showed that the expression of MBP in the PFC region of the rat brain in the PCP group was significantly lower than that in the control group (P 0.05, t-test).
2. We observed the myelin sheath development of rats on the 22nd day after birth. The results showed that compared with the control group, the number of GST-pi positive cells in PFC area of PCP group was still significantly decreased (P 0.05, t-test), the density of myelin bundle was significantly decreased (P 0.05, t-test), and the expression of MB P was still significantly lower than that of the control group (P 0.05, t-test). But the myelin sheath bundles in the PFC area of the control group and the PCP group were more dense and more extensive than those on the 16th day after birth, suggesting that myelin/oligodendrocytes were developing rapidly during this period.
3. We observed the myelin sheath development on the 32nd day after birth in rats. The results showed that the expression of MB P in PFC region of PCP group was significantly lower than that of control group (P 0.05, t-test), but there was no significant difference in the number of GST-pi positive cells and the density of myelin bundle between the two groups (P 0.05). In addition, electron microscopy showed that local degradation of the myelin sheath and formation of dense interlaminar bodies could be seen in some parts of the myelin sheath in the PCP group.
4. In order to evaluate the schizophrenia-like behavior induced by PCP intervention, the spontaneous activity and PPI of rats on the 30t h and 31st days after birth were measured. The results showed that the spontaneous activity of rats in PCP intervention group was significantly higher than that in control group (P 0.05, t-test), and PCP intervention had a significant effect on PPI [F (1,34) = 13.48, P = 0.0008], Post-h OC analysis showed that compared with the control group, the PPI (%) of the PCP group decreased significantly at PP8 and PP16 levels (P 0.05).
In the second part of the experiment, we found that quetiapine at a dose of 10 mg/kg did not ameliorate myelin dysplasia caused by PCP, nor did it ameliorate the damage of PPI associated with abnormal myelin sheath that reflects cognitive symptoms of schizophrenia, but could alleviate the increase in spontaneous activity of model animals with positive symptoms of schizophrenia induced by PCP. Below:
1. The development of myelin sheath was observed on the 16th day after birth in four groups of rats. The results of one-way ANOVA showed that there were significant differences in the number of GST-pi positive cells in PFC region [F(3,12) = 5.493, P = 0.0131], and significant differences in the distribution of myelin bundles [F(3,12) = 30.93, P 0.0001], and the expression of MB P was also significantly poor. Pos-hoc analysis showed that PCP intervention resulted in a decrease in the number of GST-pi positive cells, a decrease in the distribution of myelin bundles and a decrease in the expression of MBP protein compared with the control group, but the addition of 10 mg/kg quetiapine before PCP injection could not reverse these pathological and biochemical changes (P 0.05).
2. We observed the myelin sheath development on the 32nd day after birth in four groups of rats. One-way ANOVA showed that there were significant differences in the expression of MB P only in the PFC region of the four groups of rats [F(3,12) = 23.30, P 0.0001], but in the number of GST-pi positive cells [F(3,12) = 0.6297, P = 0.6097] and the distribution range of myelin tracts [F(3,12) = 0.3711, P = 0.0001]. Post-hoc analysis showed that PCP intervention resulted in a decrease in MBP expression compared with the control group, but the addition of 10 mg/kg quetiapine before PCP injection could not reverse the change (P 0.05).
3. Spontaneous activity and PPI were measured in rats on the 30th and 31st day after birth. The results showed that there was a significant difference in spontaneous activity among the four groups [F(3,34)=3.625, P=0.0226]. PCP and/or QUE intervention had a significant effect on PPI [F(3,64)=8.235, P=0.0001]. Compared with the control group, the spontaneous activity of the PCP intervention group was significantly increased, and PP was significantly increased. I% decreased significantly, and the addition of 10 mg/kg quetiapine before PCP injection could alleviate the increase of spontaneous activity induced by PCP, but could not reverse the damage of PPI (P 0.05).
Conclusion:
After chronic administration of PCP in neonatal rats, the developmental deficiency of myelin sheath and schizophrenic-like behavior in adolescence were observed in rats, and there was a certain correlation between the two, suggesting that abnormal myelin sheath played a certain role in the pathogenesis of schizophrenia. The model could be used to study the myelin sheath/oligodendroid process in schizophrenia. At the same time, quetiapine at a dose of 10 mg/kg did not ameliorate the myelin dysplasia induced by PCP, nor did it ameliorate the damage of PPI associated with myelin dysplasia, which reflected the cognitive symptoms of schizophrenia, but could alleviate the increase in spontaneous activity of positive symptoms of schizophrenia induced by PCP.
【学位授予单位】：第四军医大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R749.3
本文编号：2241762
[Abstract]:Research purposes:
The aim of this study was to investigate whether chronic administration of phenylcycloperidine (PCP), a NMDA receptor antagonist, could induce developmental deficiency of myelin sheath and schizophrenic-like behavior during puberty in neonatal rats, thereby developing a new type of myelin sheath/oligospermia that can be used to study schizophrenia. At the same time, we selected quetiapine, an atypical antipsychotic drug with protective effect on myelin sheath damage, to observe its effect on schizophrenia-like behavior and myelin sheath abnormality induced by PCP, in order to further establish the predictive validity of the model.
Research methods:
All the experiments in this study are animal experiments, divided into two parts: the first part is the observation of myelin sheath changes and behavioral abnormalities in rats after PCP intervention, the second part is to explore whether quetiapine can reverse the PCP-induced schizophrenia-like behavior and myelin sheath abnormalities.
In the first part, the animals were randomly divided into two groups: (1) saline control group, from the second day after birth, the experimental animals (neonatal rats) were given saline subcutaneously for 14 consecutive days, until 15 days after birth, the dose of injection was 1ml/kg; (2) PCP intervention group, from the second day after birth, the experimental animals were given PCP neck for 14 consecutive days. Subcutaneous injection, PCP injection concentration of 1mg/ml, injection volume of 10mg/kg.
In the second part, the animals were randomly divided into four groups: (1) saline control group, the experimental animals were given saline subcutaneously twice daily for 14 days from the second day after birth, and the interval between the two injections was 30 minutes from the 15th day after birth. Each injection dose of saline was 1 ml/kg; (2) PCP intervention group, from the second day after birth, was given 14 consecutive days of saline and PCP subcutaneous injection of cervical, first injection of saline, then injection of PCP, the interval between the two injections was 30 minutes. The experimental animals were injected with normal saline once a day. The concentration of PCP injection was 1 mg/ml and the dosage of PCP injection was 10 mg/kg. The dosage of physiological saline was 1 ml/kg per injection. The interval between the two injections was 30 minutes. From the 16th day after birth to the 20th day after birth, the experimental animals were given quetiapine injection once a day. The concentration of quetiapine injection was 1 mg/ml and the dosage of quetiapine injection was 10 mg/kg. The animals were subcutaneously injected with quetiapine and PCP for 14 consecutive days. The interval between the two injections was 30 minutes. From the 16th day to the 20th day after birth, the animals were injected with quetiapine once a day. The concentrations of quetiapine and PCP injection were 1 mg/ml, and the doses were 10 mg/kg.
There are two aspects to observe the indexes, one is behavioral observation: (1) spontaneous activity test, used to assess the phenomenon of spontaneous activity enhancement in rats; (2) PPI test, used to assess the degree of sensorimotor gating function damage in rats. The other is the observation of myelin sheath development: using immunohistochemistry, Western blot and electron microscopy technology observation. The development of myelin sheath in PFC region of experimental animals.
RESULTS: In the first part of the experiment, after PCP intervention in neonatal rats, we found that myelin sheath defects were detected on the 16th, 22nd and 32nd day after birth in rats, mainly manifested by the decrease of the number of mature oligodendrocytes, the narrowing of myelin bundle distribution and the decrease of MBP protein expression. Ultrastructural and pathological changes of white matter were also observed on the 32nd day after birth. Behavioral tests on the 30th and 31st days after birth showed that these rats had schizophrenic behavior.
1. We observed the myelin sheath development on the 16th day after birth in rats. Firstly, compared with the normal saline control group, the number of mature oligodendrocytes (GST-pi positive cells) in the PFC region of the rat brain in the PCP group was significantly decreased (P 0.05, t-test); secondly, there was a relatively dense immunization from anti-MBP antibody in the PFC region of the rat brain slices in the control group. Compared with the control group, the density of myelin bundles in the PFC region of the rats in the PCP group decreased significantly (P 0.05, t-test), and the MBP protein in the PFC region of the brain of the experimental rats was detected by Western blot. Blot assay showed that the expression of MBP in the PFC region of the rat brain in the PCP group was significantly lower than that in the control group (P 0.05, t-test).
2. We observed the myelin sheath development of rats on the 22nd day after birth. The results showed that compared with the control group, the number of GST-pi positive cells in PFC area of PCP group was still significantly decreased (P 0.05, t-test), the density of myelin bundle was significantly decreased (P 0.05, t-test), and the expression of MB P was still significantly lower than that of the control group (P 0.05, t-test). But the myelin sheath bundles in the PFC area of the control group and the PCP group were more dense and more extensive than those on the 16th day after birth, suggesting that myelin/oligodendrocytes were developing rapidly during this period.
3. We observed the myelin sheath development on the 32nd day after birth in rats. The results showed that the expression of MB P in PFC region of PCP group was significantly lower than that of control group (P 0.05, t-test), but there was no significant difference in the number of GST-pi positive cells and the density of myelin bundle between the two groups (P 0.05). In addition, electron microscopy showed that local degradation of the myelin sheath and formation of dense interlaminar bodies could be seen in some parts of the myelin sheath in the PCP group.
4. In order to evaluate the schizophrenia-like behavior induced by PCP intervention, the spontaneous activity and PPI of rats on the 30t h and 31st days after birth were measured. The results showed that the spontaneous activity of rats in PCP intervention group was significantly higher than that in control group (P 0.05, t-test), and PCP intervention had a significant effect on PPI [F (1,34) = 13.48, P = 0.0008], Post-h OC analysis showed that compared with the control group, the PPI (%) of the PCP group decreased significantly at PP8 and PP16 levels (P 0.05).
In the second part of the experiment, we found that quetiapine at a dose of 10 mg/kg did not ameliorate myelin dysplasia caused by PCP, nor did it ameliorate the damage of PPI associated with abnormal myelin sheath that reflects cognitive symptoms of schizophrenia, but could alleviate the increase in spontaneous activity of model animals with positive symptoms of schizophrenia induced by PCP. Below:
1. The development of myelin sheath was observed on the 16th day after birth in four groups of rats. The results of one-way ANOVA showed that there were significant differences in the number of GST-pi positive cells in PFC region [F(3,12) = 5.493, P = 0.0131], and significant differences in the distribution of myelin bundles [F(3,12) = 30.93, P 0.0001], and the expression of MB P was also significantly poor. Pos-hoc analysis showed that PCP intervention resulted in a decrease in the number of GST-pi positive cells, a decrease in the distribution of myelin bundles and a decrease in the expression of MBP protein compared with the control group, but the addition of 10 mg/kg quetiapine before PCP injection could not reverse these pathological and biochemical changes (P 0.05).
2. We observed the myelin sheath development on the 32nd day after birth in four groups of rats. One-way ANOVA showed that there were significant differences in the expression of MB P only in the PFC region of the four groups of rats [F(3,12) = 23.30, P 0.0001], but in the number of GST-pi positive cells [F(3,12) = 0.6297, P = 0.6097] and the distribution range of myelin tracts [F(3,12) = 0.3711, P = 0.0001]. Post-hoc analysis showed that PCP intervention resulted in a decrease in MBP expression compared with the control group, but the addition of 10 mg/kg quetiapine before PCP injection could not reverse the change (P 0.05).
3. Spontaneous activity and PPI were measured in rats on the 30th and 31st day after birth. The results showed that there was a significant difference in spontaneous activity among the four groups [F(3,34)=3.625, P=0.0226]. PCP and/or QUE intervention had a significant effect on PPI [F(3,64)=8.235, P=0.0001]. Compared with the control group, the spontaneous activity of the PCP intervention group was significantly increased, and PP was significantly increased. I% decreased significantly, and the addition of 10 mg/kg quetiapine before PCP injection could alleviate the increase of spontaneous activity induced by PCP, but could not reverse the damage of PPI (P 0.05).
Conclusion:
After chronic administration of PCP in neonatal rats, the developmental deficiency of myelin sheath and schizophrenic-like behavior in adolescence were observed in rats, and there was a certain correlation between the two, suggesting that abnormal myelin sheath played a certain role in the pathogenesis of schizophrenia. The model could be used to study the myelin sheath/oligodendroid process in schizophrenia. At the same time, quetiapine at a dose of 10 mg/kg did not ameliorate the myelin dysplasia induced by PCP, nor did it ameliorate the damage of PPI associated with myelin dysplasia, which reflected the cognitive symptoms of schizophrenia, but could alleviate the increase in spontaneous activity of positive symptoms of schizophrenia induced by PCP.
【学位授予单位】：第四军医大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R749.3
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