【摘要】：目的 觀察選擇性損傷內(nèi)側(cè)隔核膽堿能神經(jīng)對(duì)大鼠海洛因自身給藥獲得、消退、復(fù)吸及空間學(xué)習(xí)記憶的影響；并觀察損傷內(nèi)側(cè)隔核投射至海馬腹側(cè)下托膽堿能神經(jīng)對(duì)海洛因成癮大鼠復(fù)吸及空間學(xué)習(xí)記憶的影響。 方法 實(shí)驗(yàn)一：雄性SD大鼠隨機(jī)分為損傷組（n=8）和對(duì)照組(n=7)，損傷組注射192IgG-Saporin（0.25μg）至內(nèi)側(cè)隔核（AP+0.4, ML0, DV－5.5），對(duì)照組注射等量無菌生理鹽水；注射后恢復(fù)一周，動(dòng)物進(jìn)行FR1海洛因自身給藥獲得測(cè)試(4h)，之后進(jìn)行消退(2h)和線索誘導(dǎo)的海洛因覓藥行為測(cè)試(2h)；消退2～4天后進(jìn)行海洛因誘導(dǎo)的覓藥行為恢復(fù)測(cè)試(2h)，測(cè)試前10min腹腔注射海洛因（0.25mg/kg）；之后用Morris水迷宮測(cè)試空間定位航行能力和空間探索能力觀察兩組大鼠空間學(xué)習(xí)記憶能力，并與未成癮組大鼠（n=8）進(jìn)行比較；免疫組化ABC法染色Chat陽性細(xì)胞，觀察內(nèi)側(cè)隔核膽堿能神經(jīng)元損傷程度。 實(shí)驗(yàn)二：雄性SD大鼠構(gòu)建海洛因自身給藥模型，戒斷2周；戒斷期中樞埋管至海馬腹側(cè)下托（AP+0.4, ML0, DV－5.5），隨機(jī)分為損傷組（n=7）和對(duì)照組（n=6），損傷組雙側(cè)注射192IgG-Saporin（每側(cè)0.25μg），對(duì)照組注射等量無菌鹽水；一周后進(jìn)行海洛因覓藥行為測(cè)試，消退2～4天后進(jìn)行海洛因誘導(dǎo)的覓藥行為測(cè)試，測(cè)試前10min腹腔注射海洛因（0.25mg/kg）；之后兩組動(dòng)物進(jìn)行Morris水迷宮測(cè)試，，測(cè)試后動(dòng)物用免疫組化觀察膽堿能神經(jīng)的損傷程度。 結(jié)果 實(shí)驗(yàn)一：內(nèi)側(cè)隔核膽堿能神經(jīng)損傷后在海洛因自身給藥訓(xùn)練的獲得測(cè)試中的有效鼻觸數(shù)較對(duì)照組沒有顯著性差異，海洛因給藥次數(shù)在前期沒有差異，隨著訓(xùn)練時(shí)間延長(zhǎng)，損傷組給藥次數(shù)顯著高于對(duì)照組（P＜0.05）；在消退訓(xùn)練和線索誘導(dǎo)的海洛因覓藥行為測(cè)試中兩組的觸鼻數(shù)沒有顯著性差異；而海洛因誘導(dǎo)的覓藥行為測(cè)試中，損傷組有效觸鼻數(shù)（2h）較對(duì)照組顯著升高（P＜0.05）；Morris水迷宮測(cè)試中損傷組和對(duì)照組潛伏期、總運(yùn)動(dòng)路程和穿越平臺(tái)次數(shù)沒有顯著性差異，但兩組在定位航行試驗(yàn)和空間探索試驗(yàn)中表現(xiàn)均差于未成癮組大鼠（P＜0.05）。 實(shí)驗(yàn)二：海馬腹側(cè)下托損傷組和對(duì)照組在線索誘導(dǎo)的海洛因覓藥行為測(cè)試和海洛因誘導(dǎo)的覓藥行為測(cè)試中的有效鼻觸數(shù)沒有顯著性差異；Morris水迷宮測(cè)試中兩組潛伏期、總運(yùn)動(dòng)路程、平均速度和穿越平臺(tái)次數(shù)也沒有顯著性差異。 結(jié)論 內(nèi)側(cè)隔核膽堿能神經(jīng)損傷可增加海洛因自身給藥行為，促進(jìn)海洛因誘導(dǎo)的覓藥行為恢復(fù)，可見內(nèi)側(cè)膽堿能神經(jīng)損傷改變了海洛因的獎(jiǎng)賞效應(yīng)，促進(jìn)了對(duì)海洛因的渴求，提示膽堿能神經(jīng)可能對(duì)藥物獎(jiǎng)賞和復(fù)吸有一定的調(diào)節(jié)作用。內(nèi)側(cè)隔核膽堿能神經(jīng)損傷大鼠在海洛因誘導(dǎo)的覓藥行為測(cè)試中表現(xiàn)出后期覓藥行為增強(qiáng)，提示或因抑制控制能力減弱。海洛因成癮損害了正常的空間學(xué)習(xí)記憶功能，或是內(nèi)側(cè)隔核膽堿能神經(jīng)大鼠海洛因成癮后的空間學(xué)習(xí)記憶與對(duì)照組沒有顯著性差異的原因。內(nèi)側(cè)隔核投射至腹側(cè)下托的膽堿能損傷對(duì)海洛因復(fù)吸行為沒有影響，提示內(nèi)側(cè)隔核投射至腹側(cè)下托的膽堿能神經(jīng)投射可能不參與海洛因復(fù)吸過程。
[Abstract]:objective
The effects of selective injury of the cholinergic nerve in the medial septal nucleus on the acquisition, regression, relapse and spatial learning and memory of heroin-addicted rats were observed.
Method
Experiment 1: Male SD rats were randomly divided into injury group (n=8) and control group (n=7). Injury group was injected 192IgG-Saporin (0.25 ug) to medial septal nucleus (AP+0.4, ML0, DV-5.5), and control group was injected with the same amount of sterile saline. After one week of recovery, the animals were tested for FR1 heroin self-administration (4h), and then subsided (2h) and cue inducement. Heroin-induced drug-seeking behavior recovery test (2h) was performed 2-4 days after withdrawal. Heroin (0.25mg/kg) was injected intraperitoneally 10 minutes before withdrawal. Morris water maze was used to test spatial navigation ability and spatial exploration ability to observe the spatial learning and memory ability of rats in both groups, and compared with the non-addicted group. The Chat positive cells were stained by ABC immunohistochemistry to observe the degree of injury of cholinergic neurons in the medial septal nucleus.
Experiment 2: Male SD rats were randomly divided into injury group (n = 7) and control group (n = 6), bilateral injection of 192 IgG-Saporin (0.25 UG on each side) and control group (0.25 UG on each side) with the same amount of sterile saline, and heroin foraging was performed one week later. Heroin-induced drug-seeking behavior was tested 2-4 days after withdrawal, and heroin (0.25 mg/kg) was injected intraperitoneally 10 minutes before withdrawal. Morris water maze test was performed in both groups. The degree of cholinergic nerve injury was observed by immunohistochemistry.
Result
Experiment 1: There was no significant difference in the number of effective nasal contacts in the test of heroin self-administered training after medial septal nucleus cholinergic nerve injury compared with the control group. There was no difference in the number of heroin administered in the earlier period. With the extension of training time, the number of drug administered in the injury group was significantly higher than that in the control group (P < 0.05). There was no significant difference in the number of contact noses between the two groups in heroin seeking behavior test, but the number of effective contact noses (2h) in the injury group was significantly higher than that in the control group (P However, the performance of the two groups was worse than that of the non-addicted group (P<0.05).
Experiment 2: There was no significant difference in the number of effective nasal contacts between the ventral hypothalamus injury group and the control group in the wire-induced heroin-seeking behavior test and heroin-induced drug-seeking behavior test.
conclusion
Injury of the cholinergic nerve in the medial septal nucleus can increase heroin self-administering behavior and promote heroin-induced drug-seeking behavior recovery. It can be seen that the medial cholinergic nerve injury alters heroin reward effect and promotes heroin craving, suggesting that the cholinergic nerve may regulate drug reward and relapse. Heroin addiction impaired normal spatial learning and memory function, or the spatial learning and memory of rats with medial septal nucleus cholinergic nerve after heroin addiction were not significantly different from the control group. The cholinergic damage projected from the medial septal nucleus to the ventral inferior fossa did not affect heroin relapse behavior, suggesting that the cholinergic nerve projection from the medial septal nucleus to the ventral inferior fossa may not be involved in heroin relapse.
【學(xué)位授予單位】：寧波大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R749.64

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