本文選題：伏核 + 條件性位置偏愛實(shí)驗(yàn)��； 參考：《第四軍醫(yī)大學(xué)》2012年碩士論文

【摘要】：伏核在藥物成癮的形成中起樞紐和中轉(zhuǎn)站的作用，使其成為研究藥物成癮機(jī)制的熱點(diǎn)核團(tuán)。伏核中的哪些分子調(diào)節(jié)著伏核的生理和病理功能是廣大學(xué)者研究的重要內(nèi)容。近年來研究顯示TRPV1受體廣泛分布于中樞神經(jīng)系統(tǒng)中，且在伏核的表達(dá)尤為豐富。激活TRPV1蛋白時(shí)主要會(huì)引起Ca~(2+)等陽(yáng)離子內(nèi)流，以胞內(nèi)Ca~(2+)濃度增高的形式調(diào)節(jié)生理功能或病理機(jī)制的發(fā)生，從而導(dǎo)致所在細(xì)胞的興奮性增高。回顧文獻(xiàn)，TRPV1對(duì)伏核功能的影響研究甚少。新近研究顯示TRPV1對(duì)體質(zhì)量具有控制作用，而已有研究表明伏核與食物渴求和神經(jīng)病理性肥胖有功能上的聯(lián)系，這也為研究TRPV1對(duì)伏核功能的影響提供了思路。為探索分布于中樞神經(jīng)系統(tǒng)特別是分布于伏核中的TRPV1會(huì)有怎樣的功能作用，是否能影響伏核的功能從而影響藥物成癮，食物渴求行為，本研究采用TRPV1拮抗劑CPZ注射于包括伏核在內(nèi)的相關(guān)中樞神經(jīng)系統(tǒng)不同位點(diǎn)，以嗎啡誘導(dǎo)的條件位置偏愛測(cè)試及大鼠體質(zhì)量和脂肪積累測(cè)量?jī)煞N實(shí)驗(yàn)方案，探索伏核中的TRPV1部分生理功能，為臨床治療藥物成癮及神經(jīng)病理性肥胖提供科學(xué)的理論依據(jù)。 方法： 1．不同劑量的CPZ在嗎啡戒斷1W和3W注射于雙側(cè)伏核、單側(cè)伏核、雙側(cè)背側(cè)紋狀體，雙側(cè)伏核單側(cè)偏離靶點(diǎn)處，觀察不同劑量不同注射位點(diǎn)CPZ對(duì)大鼠mCPP影響情況。 2．觀察記錄以上測(cè)量組大鼠活動(dòng)度的情況。 3．不同劑量的CPZ在嗎啡戒斷1W注射于雙側(cè)伏核、雙側(cè)背側(cè)紋狀體，雙側(cè)伏核偏離靶點(diǎn)處，記錄各組大鼠體質(zhì)量在注射前、注射后短期（1W）以及注射后長(zhǎng)期（3W）的變化情況。 4．記錄完成后解剖各組大鼠觀察體脂含量的差異，了解各處理組與對(duì)照組相比脂肪積累的情況。 結(jié)果： 1．TRPV1拮抗劑CPZ作用于雙側(cè)伏核能夠成功消退大鼠mCPP，，并且維持消退的時(shí)程和CPZ劑量存在劑量依賴性，較高量CPZ能夠更長(zhǎng)時(shí)間維持mCPP消退狀態(tài)。 2．CPZ不能影響大鼠的活動(dòng)度，提示活動(dòng)度對(duì)嗎啡誘導(dǎo)的條件位置偏愛實(shí)驗(yàn)不構(gòu)成干擾。 3．作用于雙側(cè)伏核的CPZ可以有效抑制大鼠體質(zhì)量的增長(zhǎng)，并且抑制的時(shí)程與劑量高低存在依賴性，較高劑量CPZ可以起到更長(zhǎng)的抑制效果。 4．只有較高劑量CPZ作用于雙側(cè)伏核會(huì)對(duì)脂肪積累產(chǎn)生明顯的抑制作用。 結(jié)論： 1．阻斷伏核中的TRPV1可以有效抑制嗎啡的成癮作用，表現(xiàn)為mCPP的消退。TRPV1可能影響了伏核的興奮性，是影響伏核發(fā)揮其藥物渴求功能的重要分子。 2．阻斷伏核中的TRPV1可有效抑制大鼠體質(zhì)量的增長(zhǎng)。TRPV1對(duì)體質(zhì)量和脂肪積累的影響可能是由于分布在伏核內(nèi)的TRPV1改變伏核的興奮性從而影響自然獎(jiǎng)賞環(huán)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.
【學(xué)位授予單位】：第四軍醫(yī)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

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 秦伯益;戒毒現(xiàn)狀縱橫談[J];中國(guó)藥物依賴性雜志;1999年02期

本文編號(hào)：2059410