海馬—前額葉回路在嗎啡成癮記憶中的作用和鬼針草醇提物的神經(jīng)行為效應(yīng)
發(fā)布時間：2018-11-13 09:03
【摘要】：藥物成癮(心理成癮)是一種牢固的藥物相關(guān)記憶,稱為成癮記憶(addiction memory)。海馬(hippocampus,HP)-前額葉(prefrontal cortex,PFC)回路是空間記憶的關(guān)鍵回路,但在成癮記憶中的作用未明。首先探討了該回路在大鼠嗎啡條件位置偏愛(conditioned place preference,CPP)表達(dá)、消退及正常記憶、抑郁、焦慮等情緒中的作用。采用恒定劑量法注射嗎啡(10 mg/kg)連續(xù)8 d,建立CPP成癮模型后,向腦內(nèi)注射海人藻酸(Kaninic acid,KA),單側(cè)損毀大鼠腹側(cè)海馬(ventral hippocampus,VH)和PFC下邊緣區(qū)(infralimbic area,IL)或前邊緣區(qū)(prelimbic area,PL):同側(cè)PL和VH(VH-PL)、異側(cè)PL和VH(VH/PL,損毀VH→PL回路;損毀后進(jìn)行表達(dá)測試);同側(cè)IL和VH(VH-IL),異側(cè)IL和VH(VH/IL,損毀VH→IL回路;表達(dá)測試后再損毀)。術(shù)后測試其在CPP表達(dá)、消退、點(diǎn)燃中的分?jǐn)?shù),再進(jìn)行被動回避、強(qiáng)迫游泳、Morris水迷宮實(shí)驗(yàn)和組織學(xué)檢查。結(jié)果:(1)組織學(xué)檢查:與假手術(shù)組(Sham)相比,VH、IL、VH區(qū)域神經(jīng)元出現(xiàn)缺失,但區(qū)域外正常。(2)CPP表達(dá):與Sham相比,VH/PL損毀導(dǎo)致CPP得分減少。(3)CPP消退:Sham組未見消退,而VH-IL、VH/IL損傷組分?jǐn)?shù)均減少。(4)CPP點(diǎn)燃:點(diǎn)燃后,VH-PL、VH/PL和VH/IL組分?jǐn)?shù)處于隨機(jī)水平,而VH-IL組分?jǐn)?shù)顯著升高。(5)被動回避:除VH/PL組測試期的潛伏期與Sham類似,其余各損毀組潛伏期顯著增加。(6)強(qiáng)迫游泳:各損毀組的不動時間等指標(biāo)與Sham無明顯差異。(7)水迷宮:各組穿越平臺象限次數(shù)、停留時間等方面無顯著差異。本章重要發(fā)現(xiàn)是:大鼠嗎啡CPP成癮記憶表達(dá)依賴于VH→PL回路,VH→PL回路是HP-PFC回路中參與嗎啡成癮記憶表達(dá)的關(guān)鍵回路。之后我們探討了鬼針草(Bidens pilosa L.,BP)醇提物(ethanol extract of BP,EBP)對大鼠記憶、情緒行為的影響及離體回腸和主動脈環(huán)平滑肌收縮功能的影響。按四個劑量(0 mg/kg(對照)、25 mg/kg(低)、50 mg/kg(中)和100 mg/kg(高))飼喂大鼠1個月,然后觀察其曠場、被動回避和Morris水迷宮表現(xiàn),并觀察EBP對對照組大鼠離體回腸段和主動脈環(huán)平滑肌收縮的影響。結(jié)果:(1)曠場:大鼠進(jìn)入中央?yún)^(qū)域的潛伏期、速度、路程均無顯著性差異,而進(jìn)入中央?yún)^(qū)域的次數(shù)反而比對照組低。(2)被動回避:各組測試潛伏期,與自身訓(xùn)練期相比,均有顯著性提高,但50mg/kg、100mg/kg組與對照組相比有升高趨勢,但無顯著差異。(3)水迷宮:較對照組,給藥組找平臺時間隨劑量增高而減少的趨勢,其中50mg/kg組進(jìn)入平臺次數(shù)增加,說明EBP對空間記憶促進(jìn)作用。(4)EBP使回腸收縮,且高劑量使腎上腺素(E)舒張的腸段收縮,阿托品不能拮抗EBP的收縮作用,說明EBP使腸段收縮并不是通過乙酰膽堿(ACh)M受體,而可能是通過E的β類受體信號途徑起作用。(5)高劑量EBP使主動脈環(huán)舒張;ACh不能拮抗腎上腺素收縮動脈環(huán)的效應(yīng)而EBP可以使其舒張;EBP所致舒張效應(yīng)不能被阿托品拮抗。因此EBP也不是通過ACh M受體舒張動脈血管的。本文的創(chuàng)新點(diǎn)是:1.首次發(fā)現(xiàn),VH-PL回路是大鼠嗎啡CPP表達(dá)的關(guān)鍵回路。2.鬼針草(BP)具有一定的記憶促進(jìn)作用,可促進(jìn)腸道平滑肌收縮、血管平滑肌舒張,但并非通過其擬膽堿機(jī)制發(fā)揮作用。
[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.
【學(xué)位授予單位】：云南師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：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.
【學(xué)位授予單位】：云南師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R749.6
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