芋螺毒素类似物拮抗吗啡诱导小鼠条件性位置偏爱及调节nNOS表达的研究

发布时间：2018-02-11 23:31

本文关键词： 芋螺毒素类似物 nNOS 吗啡条件性位置偏爱奖赏效应　出处：《浙江大学》2014年硕士论文　论文类型：学位论文

【摘要】：1.目的在实验室前期研究的基础上,验证芋螺毒素类似物[Glu3,4,7,10,14]-Conantoki n-G(Glu-Con-G).[Glu3,4,7,10,14]-Conantokin-G[1-11](Glu-Con-G[1-11])和[Glu3,4,7,10,14]-Conantokin-G[S16Y](Glu-Con-G[S16Y])抗吗啡精神依赖的作用,观察吗啡成瘾小鼠海马脑区nNOS表达水平的变化,探讨其在吗啡成瘾过程中可能的作用机制,为进一步设计、筛选抗吗啡依赖的芋螺毒素类似物提供理论和实验依据。 2.实验方法采用清洁级雄性昆明种小鼠,用CPP模型检测吗啡成瘾小鼠行为学改变,用Western blotting检测目标蛋白变化。 3.结果 CPP实验结果表明,单次侧脑室注射120、240、480、960pmol Glu-Con-G,120、240、480pmol Glu-Con-G[1-11]和480、960pmol Glu-Con-G[S16Y]可以抑制吗啡诱导小鼠的CPP表达和复燃,且所给剂量均不影响小鼠的运动活性和探索行为。 Western blotting实验结果显示,一定剂量的Glu-Con-G、Glu-Con-G [1-11]、Glu-Con-G[S16Y]可以抑制吗啡成瘾小鼠海马脑区n N O S表达的增加。 4.结论 1.侧脑室注射单次给予120、240、480、960pmol Glu-Con-G,120.240、480pmol Glu-Con-G[1-11]和480、960pmol Glu-Con-G[S16Y]可抑制吗啡诱导小鼠的CPP的表达和复燃； 2.所给剂量的三种芋螺毒素类似物,在CPP建立和复燃阶段,可以抑制长期吗啡处理引起的成瘾小鼠海马脑区n N0S蛋白含量的增加； 3.所给剂量均不影响小鼠的运动活性和探索行为； 4.Glu-Con-G[1-11]药效较优,值得进一步成药性研究。
[Abstract]:1. Purpose. Based on previous laboratory studies, the effects of Conantokin-G [Glu-Conantokin-G] -Conantokin-14 [Glu-Conantokin-G] -Conantokin-G [1-11] Glu-Con-G [1-11] Glu-Con-G [1-11] and [Glu3A47101014] -Conantokin-G [S16Y] on morphine dependence were verified. To explore the possible mechanism of morphine addiction and to provide theoretical and experimental basis for the further design and screening of antimorphine dependent conotoxin analogues. 2. Experimental methods. CPP model was used to detect the behavioral changes of morphine addicted mice and Western blotting was used to detect the changes of target protein. 3. Results. The results of CPP experiment showed that single intracerebroventricular injection of 120,240mol Glu-Con-Gan 120,240 pmol Glu-Con-G [1-11] and 480,960pmol Glu-Con-G [S16Y] could inhibit the expression and recurrence of CPP in mice induced by morphine, and the dose given did not affect the motor activity and exploratory behavior of mice. The results of Western blotting experiment showed that Glu-Con-G [1-11] Glu-Con-G [S16Y] could inhibit the increase of nNOs expression in hippocampus of morphine addicted mice. 4. Conclusions. 1. Intracerebroventricular injection of 120,240U 480,960pmol Glu-Con-Gan 120.240U 480pmol Glu-Con-G [1-11] and 480,960pmol Glu-Con-G [S16Y] inhibited the expression and recurrence of CPP in mice induced by morphine. 2. The three conotoxin analogues at the given dose could inhibit the increase of nN0S protein content in hippocampus of addictive mice induced by long-term morphine treatment at the stage of CPP establishment and recrudescence. 3. The dose did not affect the motor activity and exploration behavior of mice. 4. Glu-Con-G [1-11] has better pharmacodynamics, which is worthy of further study.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R994

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