本文選題：嗎啡依賴 + 條件性位置厭惡　； 參考：《新鄉(xiāng)醫(yī)學(xué)院》2013年碩士論文

【摘要】：背景 藥物依賴涉及到中樞神經(jīng)系統(tǒng)功能廣泛變化。研究提示5-HT系統(tǒng)與藥物依賴有密切關(guān)系,5-HT能神經(jīng)系統(tǒng)對(duì)腦內(nèi)動(dòng)機(jī)相關(guān)的獎(jiǎng)賞環(huán)路調(diào)節(jié)可能是藥物依賴中神經(jīng)機(jī)制之一。 目的 測定慢性嗎啡依賴大鼠條件性位置厭惡(CPA)模型建立前后、消退后及重建后伏隔核殼區(qū)細(xì)胞外液5-HT、5-HIAA7(?)平變化,初步探討嗎非依賴的神經(jīng)生化機(jī)制。 方法 1.69只SD大鼠隨機(jī)分為研究組：慢性嗎啡注射+納洛酮催癮組(morphine+naloxone,MN);對(duì)照組：慢性嗎啡注射+生理鹽水“催癮注射”組(morphine+saline,MS)慢性生理鹽水注射+納洛酮催癮組(saline+naloxone,SN)每組23只。 2.采用連續(xù)6.5天嗎啡注射(10mg/kg,bid,IP)一次納洛酮催癮(0.3mg/kg,IP),同時(shí)與自制的條件性位置訓(xùn)練箱搭配建立CPA模型。 3.用微透析的方法分別在timel(微透析套管針植入術(shù)后3-5天),time2(Day59:00AM嗎啡/生理鹽水注射后30min),time3(Day5CPA行為訓(xùn)練后90min),time4(Day6納洛酮注射后40min),time5(day7CPA測評(píng)后90min),time6(最后一次消退行為訓(xùn)練后90min),time7(Day14重建行為訓(xùn)練后90min)透出伏隔核殼區(qū)的細(xì)胞外液。 4.用高效液相色譜-電化學(xué)方法檢測透析液中5-HT及其代謝產(chǎn)物5-HIAA濃度。 結(jié)果 1.慢性嗎啡注射與納洛酮催癮搭配(MN組)可成功建立CPA大鼠模型,表現(xiàn)出明顯的仄惡動(dòng)機(jī),對(duì)伴藥側(cè)表現(xiàn)出明顯的回避,CPA建立之后的大鼠經(jīng)過連續(xù)7天的消退訓(xùn)練后CPA可以成功消退,消退后的CPA大鼠藥物點(diǎn)燃時(shí),可再次重建。 2.嗎啡慢性注射后,MS組和MN組將大鼠伏隔核殼區(qū)的5-HT、5-HIAA水平高于對(duì)照組(P0.05)；注射納洛酮后MN組5-HT、5-HIAA濃度明顯降低(P0.01)；消退訓(xùn)練后,MN組5-HT、5-HIAA水平顯著升高(P0.01)；藥物點(diǎn)燃納洛酮催癮CPA重建后,MN組5-HT、5-HIAA水平顯著降低(P0.01)。 結(jié)論 伏隔核殼區(qū)內(nèi)5-HT參與嗎啡依賴戒斷所致CPA相關(guān)中樞厭惡動(dòng)機(jī),提示通過對(duì)5-HT的代謝和傳遞來改變中樞動(dòng)機(jī)狀態(tài),可能是阿片依賴的臨床治療的潛在靶點(diǎn)之一。
[Abstract]:Background

The study suggests that the 5 - HT system is closely related to drug dependence , and the 5 - HT system may be one of the neural mechanisms in drug dependence .

Purpose

The changes of 5 - HT , 5 - HIAA7 ( ? ) levels in extracellular fluid of the isolated nuclear shell were measured before and after the establishment of chronic morphine dependent rat conditioned position aversion ( CPA ) model .

method

1.69 SD rats were randomly divided into two groups : morphine + naloxone ( MN ) and morphine + naloxone ( MN ) ; control group : morphine + saline ( MS ) + saline + naloxone ( SN ) group ( n = 23 ) .

2 . A continuous 6.5 - day morphine injection ( 10 mg / kg , bid , IP ) was used to treat naloxone ( 0.3mg / kg , IP ) , and the CPA model was established with the self - made conditioned place training box .

3 . The extracellular fluid of the isolated nuclear shell area was measured at timel ( 3 - 5 days after micro - dialysis trocar implantation ) , time2 ( Day59 : 00 AM morphine / physiological saline ) , time3 ( Day5 CPA behavior training 90 min ) , time5 ( 90 min after day 6 naloxone injection ) , time6 ( 90 min after the last regression behavior ) , time7 ( 90 min after the training of Day14 reconstruction ) .

4 . 5 - HT and its metabolite 5 - HIAA concentration were determined by HPLC - electrochemical method .

Results

1 . The rats model of CPA was successfully established by chronic morphine injection and naloxone ( MN group ) .

2 . After chronic morphine injection , the levels of 5 - HT and 5 - HIAA were higher in MS group and MN group than in the control group ( P0.05 ) .
The concentration of 5 - HT and 5 - HIAA in MN group decreased significantly after naloxone injection ( P0.01 ) .
The levels of 5 - HT and 5 - HIAA in MN group increased significantly ( P0.01 ) .
The 5 - HT and 5 - HIAA levels were significantly lower in MN group ( P0.01 ) .

Conclusion

5 - HT is involved in the central aversion to morphine dependence induced by morphine dependence . It suggests that the metabolism and transmission of 5 - HT may be one of the potential targets for clinical treatment of opioid dependence .
【學(xué)位授予單位】：新鄉(xiāng)醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R749.6

【參考文獻(xiàn)】

相關(guān)期刊論文 前9條

1 谷建平,叢斌,劉東剛,谷振勇,畢海濤,朱桂云;嗎啡依賴和戒斷大鼠中樞cAMP和cGMP含量的變化[J];中國法醫(yī)學(xué)雜志;2004年05期

2 王云;岳云;史琳;;腦和脊髓微透析技術(shù)的理論、方法和應(yīng)用[J];國際麻醉學(xué)與復(fù)蘇雜志;2007年05期

3 莊宗;趙旭東;史繼新;;微透析技術(shù)在神經(jīng)外科中的應(yīng)用[J];醫(yī)學(xué)研究生學(xué)報(bào);2010年08期

4 李青;張?zhí)N琨;;微透析技術(shù)在運(yùn)動(dòng)性中樞疲勞研究中的應(yīng)用[J];南京體育學(xué)院學(xué)報(bào)(自然科學(xué)版);2010年01期

5 俞晨;徐又佳;張志琳;董啟榕;鄭祖根;張震東;馬勇;高慧;;腦微透析法研究大鼠脊髓損傷后腦內(nèi)興奮性氨基酸的動(dòng)態(tài)變化[J];蘇州大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2006年06期

6 李健;陳勁草;;腦微透析法監(jiān)測動(dòng)脈瘤術(shù)中臨時(shí)阻斷對(duì)腦局部興奮性氨基酸水平的影響[J];實(shí)用醫(yī)學(xué)雜志;2006年08期

7 刁秋霞;李積勝;;阿片依賴相關(guān)神經(jīng)遞質(zhì)研究進(jìn)展[J];武警醫(yī)學(xué)院學(xué)報(bào);2008年02期

8 王杰瓊;張惠云;;微透析技術(shù)結(jié)合色-質(zhì)聯(lián)用檢測細(xì)胞外液神經(jīng)遞質(zhì)研究進(jìn)展[J];醫(yī)學(xué)綜述;2011年07期

9 劉彩誼;李勇輝;白云靜;隋南;;杏仁中央核NMDA受體對(duì)急性嗎啡依賴大鼠戒斷誘發(fā)條件性位置厭惡的影響[J];中國心理衛(wèi)生雜志;2008年02期

，

本文編號(hào)：2044219