伏核中的TRPV1对大鼠吗啡依赖和中枢性体质量调节的影响

发布时间：2018-06-24 01:43

本文选题：伏核 + 条件性位置偏爱实验　；参考：《第四军医大学》2012年硕士论文

【摘要】：伏核在药物成瘾的形成中起枢纽和中转站的作用，使其成为研究药物成瘾机制的热点核团。伏核中的哪些分子调节着伏核的生理和病理功能是广大学者研究的重要内容。近年来研究显示TRPV1受体广泛分布于中枢神经系统中，且在伏核的表达尤为丰富。激活TRPV1蛋白时主要会引起Ca~(2+)等阳离子内流，以胞内Ca~(2+)浓度增高的形式调节生理功能或病理机制的发生，从而导致所在细胞的兴奋性增高。回顾文献，TRPV1对伏核功能的影响研究甚少。新近研究显示TRPV1对体质量具有控制作用，而已有研究表明伏核与食物渴求和神经病理性肥胖有功能上的联系，这也为研究TRPV1对伏核功能的影响提供了思路。为探索分布于中枢神经系统特别是分布于伏核中的TRPV1会有怎样的功能作用，是否能影响伏核的功能从而影响药物成瘾，食物渴求行为，本研究采用TRPV1拮抗剂CPZ注射于包括伏核在内的相关中枢神经系统不同位点，以吗啡诱导的条件位置偏爱测试及大鼠体质量和脂肪积累测量两种实验方案，探索伏核中的TRPV1部分生理功能，为临床治疗药物成瘾及神经病理性肥胖提供科学的理论依据。方法： 1．不同剂量的CPZ在吗啡戒断1W和3W注射于双侧伏核、单侧伏核、双侧背侧纹状体，双侧伏核单侧偏离靶点处，观察不同剂量不同注射位点CPZ对大鼠mCPP影响情况。 2．观察记录以上测量组大鼠活动度的情况。 3．不同剂量的CPZ在吗啡戒断1W注射于双侧伏核、双侧背侧纹状体，双侧伏核偏离靶点处，记录各组大鼠体质量在注射前、注射后短期（1W）以及注射后长期（3W）的变化情况。 4．记录完成后解剖各组大鼠观察体脂含量的差异，了解各处理组与对照组相比脂肪积累的情况。结果： 1．TRPV1拮抗剂CPZ作用于双侧伏核能够成功消退大鼠mCPP，，并且维持消退的时程和CPZ剂量存在剂量依赖性，较高量CPZ能够更长时间维持mCPP消退状态。 2．CPZ不能影响大鼠的活动度，提示活动度对吗啡诱导的条件位置偏爱实验不构成干扰。 3．作用于双侧伏核的CPZ可以有效抑制大鼠体质量的增长，并且抑制的时程与剂量高低存在依赖性，较高剂量CPZ可以起到更长的抑制效果。 4．只有较高剂量CPZ作用于双侧伏核会对脂肪积累产生明显的抑制作用。结论： 1．阻断伏核中的TRPV1可以有效抑制吗啡的成瘾作用，表现为mCPP的消退。TRPV1可能影响了伏核的兴奋性，是影响伏核发挥其药物渴求功能的重要分子。 2．阻断伏核中的TRPV1可有效抑制大鼠体质量的增长。TRPV1对体质量和脂肪积累的影响可能是由于分布在伏核内的TRPV1改变伏核的兴奋性从而影响自然奖赏环路引起的。
[Abstract]:Nucleus accumbens plays the role of hub and transit station in the formation of drug addiction, which makes it a hot nucleus to study the mechanism of drug addiction. Which molecules in nucleus accumbens regulate the physiological and pathological functions of nucleus accumbens are the important contents of many scholars. Recent studies have shown that TRPV1 receptors are widely distributed in the central nervous system, especially in nucleus accumbens. Activation of TRPV1 protein can mainly induce cationic influx such as Ca ~ (2), and regulate physiological function or pathological mechanism in the form of increased intracellular Ca ~ (2) concentration, resulting in the increase of excitability of the host cell. The effect of TRPV1 on nucleus accumbens function was reviewed. Recent studies have shown that TRPV1 can control the body mass, while some studies have shown that the nucleus accumbens has a functional relationship with food craving and neuropathic obesity, which provides a way to study the effect of TRPV1 on the function of nucleus accumbens. In order to explore the function of TRPV1 distributed in the central nervous system, especially in nucleus accumbens, whether it can affect the function of nucleus accumbens and thus affect drug addiction, food craving behavior. In this study, TRPV1 antagonist CPZ was injected into different sites of central nervous system, including nucleus accumbens. Morphine induced conditioned place preference test and measurement of body mass and fat accumulation in rats were used. To explore the physiological function of TRPV1 in nucleus accumbens and to provide a scientific basis for the treatment of drug addiction and neuropathic obesity. Methods: 1. Different doses of CPZ were injected into bilateral nucleus accumbens, unilateral nucleus accumbens, bilateral dorsal striatum and bilateral nucleus accumbens at 1W and 3W after morphine withdrawal. The effects of CPZ at different doses on mCPP in rats were observed. 2. The activity of rats in the above group was recorded. 3. Different doses of CPZ were injected into bilateral nucleus accumbens at 1 week after withdrawal from morphine withdrawal. Bilateral dorsal striatum, bilateral nucleus accumbens deviated from the target, and the body mass of each group was recorded before injection. The changes of short-term (1 W) and long term (3 W) after injection. 4. Observe the difference of body fat content and understand the fat accumulation in each treatment group compared with the control group. 4. Results: 1. TRPV1 antagonist CPZ could successfully attenuate mCPP in bilateral nucleus accumbens in a dose-dependent manner. A higher dose of CPZ could maintain the extinction of mCPP for a longer period of time. 2. CPZ could not affect the activity of rats. 3. CPZ acting on bilateral nucleus accumbens could effectively inhibit the growth of body mass in rats, and the duration of inhibition was dependent on the dose level. Higher dose of CPZ could play a longer inhibitory effect. 4. Only higher dose of CPZ on bilateral nucleus accumbens could obviously inhibit fat accumulation. Conclusion: 1. Blocking TRPV1 in nucleus accumbens can effectively inhibit morphine addiction, which is shown that the extinction of mCPP and TRPV1 may affect the excitability of nucleus accumbens. 2. Blocking TRPV1 in nucleus accumbens can effectively inhibit the growth of body mass in rats. The effect of TRPV1 on body mass and fat accumulation may be due to its distribution in nucleus accumbens. TRPV1 changes the excitability of nucleus accumbens, thus affecting the natural reward loop.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.64

【参考文献】