海马—前额叶回路在吗啡成瘾记忆中的作用和鬼针草醇提物的神经行为效应
发布时间：2018-11-13 09:03
【摘要】：药物成瘾(心理成瘾)是一种牢固的药物相关记忆,称为成瘾记忆(addiction memory)。海马(hippocampus,HP)-前额叶(prefrontal cortex,PFC)回路是空间记忆的关键回路,但在成瘾记忆中的作用未明。首先探讨了该回路在大鼠吗啡条件位置偏爱(conditioned place preference,CPP)表达、消退及正常记忆、抑郁、焦虑等情绪中的作用。采用恒定剂量法注射吗啡(10 mg/kg)连续8 d,建立CPP成瘾模型后,向脑内注射海人藻酸(Kaninic acid,KA),单侧损毁大鼠腹侧海马(ventral hippocampus,VH)和PFC下边缘区(infralimbic area,IL)或前边缘区(prelimbic area,PL):同侧PL和VH(VH-PL)、异侧PL和VH(VH/PL,损毁VH→PL回路;损毁后进行表达测试);同侧IL和VH(VH-IL),异侧IL和VH(VH/IL,损毁VH→IL回路;表达测试后再损毁)。术后测试其在CPP表达、消退、点燃中的分数,再进行被动回避、强迫游泳、Morris水迷宫实验和组织学检查。结果:(1)组织学检查:与假手术组(Sham)相比,VH、IL、VH区域神经元出现缺失,但区域外正常。(2)CPP表达:与Sham相比,VH/PL损毁导致CPP得分减少。(3)CPP消退:Sham组未见消退,而VH-IL、VH/IL损伤组分数均减少。(4)CPP点燃:点燃后,VH-PL、VH/PL和VH/IL组分数处于随机水平,而VH-IL组分数显著升高。(5)被动回避:除VH/PL组测试期的潜伏期与Sham类似,其余各损毁组潜伏期显著增加。(6)强迫游泳:各损毁组的不动时间等指标与Sham无明显差异。(7)水迷宫:各组穿越平台象限次数、停留时间等方面无显著差异。本章重要发现是:大鼠吗啡CPP成瘾记忆表达依赖于VH→PL回路,VH→PL回路是HP-PFC回路中参与吗啡成瘾记忆表达的关键回路。之后我们探讨了鬼针草(Bidens pilosa L.,BP)醇提物(ethanol extract of BP,EBP)对大鼠记忆、情绪行为的影响及离体回肠和主动脉环平滑肌收缩功能的影响。按四个剂量(0 mg/kg(对照)、25 mg/kg(低)、50 mg/kg(中)和100 mg/kg(高))饲喂大鼠1个月,然后观察其旷场、被动回避和Morris水迷宫表现,并观察EBP对对照组大鼠离体回肠段和主动脉环平滑肌收缩的影响。结果:(1)旷场:大鼠进入中央区域的潜伏期、速度、路程均无显著性差异,而进入中央区域的次数反而比对照组低。(2)被动回避:各组测试潜伏期,与自身训练期相比,均有显著性提高,但50mg/kg、100mg/kg组与对照组相比有升高趋势,但无显著差异。(3)水迷宫:较对照组,给药组找平台时间随剂量增高而减少的趋势,其中50mg/kg组进入平台次数增加,说明EBP对空间记忆促进作用。(4)EBP使回肠收缩,且高剂量使肾上腺素(E)舒张的肠段收缩,阿托品不能拮抗EBP的收缩作用,说明EBP使肠段收缩并不是通过乙酰胆碱(ACh)M受体,而可能是通过E的β类受体信号途径起作用。(5)高剂量EBP使主动脉环舒张;ACh不能拮抗肾上腺素收缩动脉环的效应而EBP可以使其舒张;EBP所致舒张效应不能被阿托品拮抗。因此EBP也不是通过ACh M受体舒张动脉血管的。本文的创新点是:1.首次发现,VH-PL回路是大鼠吗啡CPP表达的关键回路。2.鬼针草(BP)具有一定的记忆促进作用,可促进肠道平滑肌收缩、血管平滑肌舒张,但并非通过其拟胆碱机制发挥作用。
[Abstract]:Drug addiction (addiction) is a strong drug-related memory, known as an addiction memory. Hippocampus (HP)-prefrontal cortex (PFC) loop is the key loop of spatial memory, but its role in the memory of addiction is not clear. The effects of the loop on the expression, resolution and normal memory, depression and anxiety of the rat morphine conditional position preference (CPP) were discussed. After the injection of morphine (10 mg/ kg) by a constant-dose method for 8 days, a CPP-addiction model was established, and the rat-side hippocampus (VH) and the lower edge region (PL) of the rat's ventral hippocampus (VH) and the lower edge of the PFC were damaged unilaterally. Same side PL and VH (VH-PL), isoside PL and VH (VH/ PL, damage to VH and PL loop; expression test after destruction); same side IL and VH (VH-IL), isoside IL and VH (VH/ IL, damage to VH and IL loop; expression test and re-destruction). After the operation, the expression, regression and ignition of CPP were measured, and passive avoidance, forced swimming, Morris water maze test and histological examination were performed. Results: (1) Histological examination: Compared with sham operation group (Sham), the neurons of VH, IL and VH were absent but the area was normal. (2) CPP expression: The VH/ PL damage resulted in a decrease in the CPP score compared to the sham. (3) CPP resolved: sham group did not see regression, while the scores of VH-IL, VH/ IL damaged groups were reduced. (4) CPP ignition: After ignition, the scores of VH-PL, VH/ PL and VH/ IL groups were at random levels, while the scores of VH-IL groups increased significantly. (5) Passive avoidance: In addition to the incubation period of the test period of the VH/ PL group, the latent period of the remaining damaged groups was significantly increased. (6) Forced swimming: There is no significant difference between the indexes of the non-moving time of each damaged group and the Sham. (7) Water maze: there is no significant difference in the number of quadrant and residence time of each group of crossing platforms. The important finding in this chapter is that the expression of the morphine CPP is dependent on the VH and PL loop, and the VH-PL loop is the key loop involved in the expression of morphine-dependent memory in the HP-PFC loop. The effects of ethanol extract of BP and EBP on the memory and emotional behavior of the rats and the effects of the separation of the body ileum and the aortic ring smooth muscle were discussed. Four doses (0 mg/ kg (control), 25 mg/ kg (low), 50 mg/ kg (medium) and 100 mg/ kg (high)) were fed to the rat for 1 month, and the effects of EBP on the contraction of the left and the aortic rings of the rats in the control group were observed. Results: (1) There was no significant difference in the latency, the speed and the distance of the rat into the central region, and the number of times of entering the central region was lower than that of the control group. (2) Passive avoidance: There was a significant increase in the incubation period of each group, compared with the self-training period, but the concentration of 50mg/ kg and 100mg/ kg was higher than that of the control group, but there was no significant difference. (3) Water maze: Compared with the control group, the time to find the platform time in the administration group decreased with the increase of the dose, of which the number of the 50 mg/ kg group entered the platform increased, and the effect of EBP on the spatial memory was explained. (4) EBP causes the contraction of the ileum, and the high dose causes the intestinal segment of the epinephrine (E) to relax, and atropine can not antagonize the contractile effect of EBP, and it is suggested that the EBP causes the contraction of the intestinal segment not to pass through the acetylcholine (ACh) M receptor, but may be by the E-class receptor signaling pathway. (5) The high-dose EBP can relax the aortic annulus; the ACh can not antagonize the effect of the epinephrine-contraction arterial ring and the EBP can relax the aortic annulus; the relaxation effect caused by the EBP can not be antagonized by atropine. Therefore, the EBP is not the arterial blood vessel of the ACh M receptor. The innovation point of this paper is: 1. The first time, the VH-PL loop is the key loop of the expression of morphine CPP in rats. Podophyta (BP) has a certain memory-promoting effect, which can promote the contraction of the intestinal smooth muscle and the relaxation of the smooth muscle of the blood vessel.
【学位授予单位】：云南师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.6
[Abstract]:Drug addiction (addiction) is a strong drug-related memory, known as an addiction memory. Hippocampus (HP)-prefrontal cortex (PFC) loop is the key loop of spatial memory, but its role in the memory of addiction is not clear. The effects of the loop on the expression, resolution and normal memory, depression and anxiety of the rat morphine conditional position preference (CPP) were discussed. After the injection of morphine (10 mg/ kg) by a constant-dose method for 8 days, a CPP-addiction model was established, and the rat-side hippocampus (VH) and the lower edge region (PL) of the rat's ventral hippocampus (VH) and the lower edge of the PFC were damaged unilaterally. Same side PL and VH (VH-PL), isoside PL and VH (VH/ PL, damage to VH and PL loop; expression test after destruction); same side IL and VH (VH-IL), isoside IL and VH (VH/ IL, damage to VH and IL loop; expression test and re-destruction). After the operation, the expression, regression and ignition of CPP were measured, and passive avoidance, forced swimming, Morris water maze test and histological examination were performed. Results: (1) Histological examination: Compared with sham operation group (Sham), the neurons of VH, IL and VH were absent but the area was normal. (2) CPP expression: The VH/ PL damage resulted in a decrease in the CPP score compared to the sham. (3) CPP resolved: sham group did not see regression, while the scores of VH-IL, VH/ IL damaged groups were reduced. (4) CPP ignition: After ignition, the scores of VH-PL, VH/ PL and VH/ IL groups were at random levels, while the scores of VH-IL groups increased significantly. (5) Passive avoidance: In addition to the incubation period of the test period of the VH/ PL group, the latent period of the remaining damaged groups was significantly increased. (6) Forced swimming: There is no significant difference between the indexes of the non-moving time of each damaged group and the Sham. (7) Water maze: there is no significant difference in the number of quadrant and residence time of each group of crossing platforms. The important finding in this chapter is that the expression of the morphine CPP is dependent on the VH and PL loop, and the VH-PL loop is the key loop involved in the expression of morphine-dependent memory in the HP-PFC loop. The effects of ethanol extract of BP and EBP on the memory and emotional behavior of the rats and the effects of the separation of the body ileum and the aortic ring smooth muscle were discussed. Four doses (0 mg/ kg (control), 25 mg/ kg (low), 50 mg/ kg (medium) and 100 mg/ kg (high)) were fed to the rat for 1 month, and the effects of EBP on the contraction of the left and the aortic rings of the rats in the control group were observed. Results: (1) There was no significant difference in the latency, the speed and the distance of the rat into the central region, and the number of times of entering the central region was lower than that of the control group. (2) Passive avoidance: There was a significant increase in the incubation period of each group, compared with the self-training period, but the concentration of 50mg/ kg and 100mg/ kg was higher than that of the control group, but there was no significant difference. (3) Water maze: Compared with the control group, the time to find the platform time in the administration group decreased with the increase of the dose, of which the number of the 50 mg/ kg group entered the platform increased, and the effect of EBP on the spatial memory was explained. (4) EBP causes the contraction of the ileum, and the high dose causes the intestinal segment of the epinephrine (E) to relax, and atropine can not antagonize the contractile effect of EBP, and it is suggested that the EBP causes the contraction of the intestinal segment not to pass through the acetylcholine (ACh) M receptor, but may be by the E-class receptor signaling pathway. (5) The high-dose EBP can relax the aortic annulus; the ACh can not antagonize the effect of the epinephrine-contraction arterial ring and the EBP can relax the aortic annulus; the relaxation effect caused by the EBP can not be antagonized by atropine. Therefore, the EBP is not the arterial blood vessel of the ACh M receptor. The innovation point of this paper is: 1. The first time, the VH-PL loop is the key loop of the expression of morphine CPP in rats. Podophyta (BP) has a certain memory-promoting effect, which can promote the contraction of the intestinal smooth muscle and the relaxation of the smooth muscle of the blood vessel.
【学位授予单位】：云南师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.6
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