背外侧被盖核胆碱能神经对线索诱导大鼠海洛因复吸影响

发布时间：2018-04-08 11:42

本文选题：背外侧被盖核　切入点：胆碱能M_4受体　出处：《宁波大学》2012年硕士论文

【摘要】：目的：中脑腹侧被盖区（Ventral tegmental area， VTA）到伏隔核（Nucleusaccumbens， NAc）的多巴胺投射通路是目前认为药物奖赏和复吸的关键通路，乙酰胆碱（Acetylcholine，Ach）对VTA投射NAc的奖赏通路有重要调节作用，胆碱能神经主要是投射神经元，由背外侧被盖核（Laterodorsal tegmentalnucleus，LDTg）主要投射到VTA，而脚桥被盖核（Pedunculopontine tegmentalnucleus，PPTg）少量投射到VTA。本研究目的是观察LDTg胆碱能神经及胆碱能毒蕈碱受体（Muscarinic acetylcholine receptors，M受体）对线索及海洛因诱导的大鼠觅药行为复吸的影响，以期待发现新的参与海洛因复吸的中枢靶点，为临床海洛因复吸防治提供理论依据。方法：雄性SD大鼠颈静脉插管手术恢复7d后，进行固定比例FR1程序训练14d，建立海洛因自身给药模型；海洛因自身给药模型大鼠戒断14d，期间LDTg中枢立体定位，术后恢复3d；LDTg分别核团微注射胆碱酯酶抑制剂Gal及胆碱能M受体拮抗剂Sco，观察对线索诱导的海洛因复吸行为的影响；LDTg分别核团微注射胆碱能M_4受体激动剂xanomeline和胆碱能M_4受体变构增强剂vu0152100，观察对线索及海洛因诱导的大鼠复吸行为的影响。结果： 1. LDTg微量注射胆碱酯酶抑制剂Gal（3μg/μl）、Sco（0.5μg/μl）、Gal+Sco对线索诱导的海洛因复吸行为实验中，Gal组有效鼻触数明显低于正常对照组（P0.05），且Gal组有效鼻触数也明显低于Gal+Sco组（P0.01）。 2. LDTg微注射胆碱能M_4受体选择性激动剂xanomeline对线索及海洛因诱导的复吸行为实验中，xanomeline（1μg/μl）组与对照组对线索诱导的觅药行为复吸测试的有效鼻触数无统计学差异，而xanomeline （3μg/μl、10μg/μl）处理组较对照组有效鼻触数均显著减少（P0.05）； xanomeline（1μg/μl、3μg/μl）组与对照组对海洛因诱导的觅药行为复吸测试中，显示有效鼻触数明显减少具有显著差异（P0.05）。 3. LDTg微注射胆碱能M_4受体变构增强剂vu0152100对线索及海洛因诱导的复吸行为实验中，线索诱导海洛因复吸行为测试0.5h时，vu0152100组有效鼻触数明显低于正常对照组（P0.05），但1h、1.5h及2h无效鼻触数与对照组比较无统计学差异；海洛因诱导的复吸行为测试0.5h和1h时，，vu0152100组有效鼻触数明显低于正常对照组（P0.05），但1.5h和2h有效鼻触数与对照组比较无统计学差异。结论： LDTg微注射胆碱酯酶抑制剂Gal能显著抑制条件性线索诱导的大鼠海洛因觅药行为复吸，Sco则能逆转此现象；LDTg微注射胆碱能M_4受体激动剂xanomeline和变构增强剂vu0152100均能显著抑制海洛因诱导的觅药行为。结果提示LDTg胆碱能M受体参与了调节了线索及海洛因诱导的大鼠海洛因复吸过程，尤其是LDTg胆碱能M_4受体参与了线索及海洛因诱导的大鼠觅药行为复吸过程，进一步证明了LDTg投射到VTA的胆碱能神经在线索或海洛因诱导的大鼠海洛因复吸过程中发挥重要作用。
[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.
【学位授予单位】：宁波大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.64

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