本文選題：背外側(cè)被蓋核　切入點(diǎn)：膽堿能M_4受體　出處：《寧波大學(xué)》2012年碩士論文

【摘要】：目的： 中腦腹側(cè)被蓋區(qū)（Ventral tegmental area， VTA）到伏隔核（Nucleusaccumbens， NAc）的多巴胺投射通路是目前認(rèn)為藥物獎(jiǎng)賞和復(fù)吸的關(guān)鍵通路，乙酰膽堿（Acetylcholine，Ach）對(duì)VTA投射NAc的獎(jiǎng)賞通路有重要調(diào)節(jié)作用，膽堿能神經(jīng)主要是投射神經(jīng)元，由背外側(cè)被蓋核（Laterodorsal tegmentalnucleus，LDTg）主要投射到VTA，而腳橋被蓋核（Pedunculopontine tegmentalnucleus，PPTg）少量投射到VTA。本研究目的是觀察LDTg膽堿能神經(jīng)及膽堿能毒蕈堿受體（Muscarinic acetylcholine receptors，M受體）對(duì)線索及海洛因誘導(dǎo)的大鼠覓藥行為復(fù)吸的影響，以期待發(fā)現(xiàn)新的參與海洛因復(fù)吸的中樞靶點(diǎn)，為臨床海洛因復(fù)吸防治提供理論依據(jù)。 方法： 雄性SD大鼠頸靜脈插管手術(shù)恢復(fù)7d后，進(jìn)行固定比例FR1程序訓(xùn)練14d，建立海洛因自身給藥模型；海洛因自身給藥模型大鼠戒斷14d，期間LDTg中樞立體定位，術(shù)后恢復(fù)3d；LDTg分別核團(tuán)微注射膽堿酯酶抑制劑Gal及膽堿能M受體拮抗劑Sco，觀察對(duì)線索誘導(dǎo)的海洛因復(fù)吸行為的影響；LDTg分別核團(tuán)微注射膽堿能M_4受體激動(dòng)劑xanomeline和膽堿能M_4受體變構(gòu)增強(qiáng)劑vu0152100，觀察對(duì)線索及海洛因誘導(dǎo)的大鼠復(fù)吸行為的影響。 結(jié)果： 1. LDTg微量注射膽堿酯酶抑制劑Gal（3μg/μl）、Sco（0.5μg/μl）、Gal+Sco對(duì)線索誘導(dǎo)的海洛因復(fù)吸行為實(shí)驗(yàn)中，Gal組有效鼻觸數(shù)明顯低于正常對(duì)照組（P0.05），且Gal組有效鼻觸數(shù)也明顯低于Gal+Sco組（P0.01）。 2. LDTg微注射膽堿能M_4受體選擇性激動(dòng)劑xanomeline對(duì)線索及海洛因誘導(dǎo)的復(fù)吸行為實(shí)驗(yàn)中，xanomeline（1μg/μl）組與對(duì)照組對(duì)線索誘導(dǎo)的覓藥行為復(fù)吸測(cè)試的有效鼻觸數(shù)無統(tǒng)計(jì)學(xué)差異，而xanomeline （3μg/μl、10μg/μl）處理組較對(duì)照組有效鼻觸數(shù)均顯著減少（P0.05）； xanomeline（1μg/μl、3μg/μl）組與對(duì)照組對(duì)海洛因誘導(dǎo)的覓藥行為復(fù)吸測(cè)試中，顯示有效鼻觸數(shù)明顯減少具有顯著差異（P0.05）。 3. LDTg微注射膽堿能M_4受體變構(gòu)增強(qiáng)劑vu0152100對(duì)線索及海洛因誘導(dǎo)的復(fù)吸行為實(shí)驗(yàn)中，線索誘導(dǎo)海洛因復(fù)吸行為測(cè)試0.5h時(shí)，vu0152100組有效鼻觸數(shù)明顯低于正常對(duì)照組（P0.05），但1h、1.5h及2h無效鼻觸數(shù)與對(duì)照組比較無統(tǒng)計(jì)學(xué)差異；海洛因誘導(dǎo)的復(fù)吸行為測(cè)試0.5h和1h時(shí)，，vu0152100組有效鼻觸數(shù)明顯低于正常對(duì)照組（P0.05），但1.5h和2h有效鼻觸數(shù)與對(duì)照組比較無統(tǒng)計(jì)學(xué)差異。 結(jié)論： LDTg微注射膽堿酯酶抑制劑Gal能顯著抑制條件性線索誘導(dǎo)的大鼠海洛因覓藥行為復(fù)吸，Sco則能逆轉(zhuǎn)此現(xiàn)象；LDTg微注射膽堿能M_4受體激動(dòng)劑xanomeline和變構(gòu)增強(qiáng)劑vu0152100均能顯著抑制海洛因誘導(dǎo)的覓藥行為。結(jié)果提示LDTg膽堿能M受體參與了調(diào)節(jié)了線索及海洛因誘導(dǎo)的大鼠海洛因復(fù)吸過程，尤其是LDTg膽堿能M_4受體參與了線索及海洛因誘導(dǎo)的大鼠覓藥行為復(fù)吸過程，進(jìn)一步證明了LDTg投射到VTA的膽堿能神經(jīng)在線索或海洛因誘導(dǎo)的大鼠海洛因復(fù)吸過程中發(fā)揮重要作用。
[Abstract]:Objective:The dopamine pathway from ventral tegmental area (VTAA) to Nucleus accumbens (NAc) in ventral tegmental area of the mesencephalon is considered to be the key pathway for drug reward and relapse. Acetylcholine acetylcholine Ach) plays an important role in regulating the pathway of VTA projecting NAc.Cholinergic nerves were mainly projective neurons, mainly projected to VTAs from Laterodorsal tegmental nucleus (LDTg) and pedunculopontine tegmental nucleus PPTg (PPTg).The aim of this study was to observe the effects of LDTg cholinergic nerve and muscarinic acetylcholine receptor M receptor on drug seeking behavior in rats induced by heroin and to find new central targets involved in heroin relapse.To provide a theoretical basis for the prevention and treatment of heroin relapse.Methods:Male Sprague-Dawley (SD) rats were trained with fixed proportion FR1 program for 14 days after the recovery of jugular vein intubation, and the model of heroin self-administration was established, and the rats were given heroin self-administration for 14 days, during which the LDTg center was stereoscopically located.Gal and Scotch, cholinergic M receptor antagonists, were microinjected into the nucleus respectively on the 3rd day after recovery. The effect of LDTg on the heroin relapse induced by clues was observed. The microinjection of cholinergic M4 receptor agonist xanomeline and choline respectively into LDTg nucleus was observed.To observe the effect of Vu0152100 on the relapse behavior of rats induced by heroin and clue.Results:1.2.LDTg microinjection of cholinergic M4-receptor selective agonist xanomeline had no significant difference in the effective nasal contact number of cue-induced drug seeking behavior relapse test between the two groups and the control group (1 渭 g / 渭 l).3.LDTg microinjection of cholinergic M4 receptor enhancer vu0152100 on clues and heroin induced relapse behavior,The number of effective nasal contacts in the vu0152100 group was significantly lower than that in the normal control group at 0.5 h, but there was no significant difference between the control group and the control group at 1.5 h and 2 h.The number of effective nasal contacts in Vu0152100 group was significantly lower than that in the normal control group at 0.5 h and 1 h, but there was no significant difference between 1.5 h and 2 h in the effective nasal contact number between the control group and the control group.Conclusion:LDTg microinjection of cholinesterase inhibitor Gal could significantly inhibit conditioned cue-induced heroin seeking behavior in rats. Sco could reverse this phenomenon. LDTg microinjection of cholinergic M4 receptor agonist xanomeline and metamorphic enhancer vu0152100 could significantly inhibit this phenomenon.Heroin-induced drug-seeking behavior.The results suggested that LDTg cholinergic M receptor was involved in the process of heroin relapse induced by heroin and clue, especially that LDTg cholinergic M _ 4 receptor was involved in the course of drug seeking behavior of rats induced by heroin, especially LDTg cholinergic M _ 4 receptor.It is further demonstrated that cholinergic nerves projected by LDTg to VTA play an important role in the process of heroin relapse induced by clue or heroin in rats.
【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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