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

【摘要】：目的 通過測定嗎啡依賴大鼠納洛酮催癮CPA建立、消退及重建不同階段伏隔核殼區(qū)多巴胺(dopamine)及其代謝產(chǎn)物3,4二羥基苯乙酸(dihydroxyphenyl acetic acid, DOPAC)濃度的變化情況,探討嗎啡依賴負(fù)性強(qiáng)化的神經(jīng)生化機(jī)制。 方法 1、69只SPF級雄性(Sprage-Dawley)大鼠隨機(jī)分為實驗組(嗎啡+納洛酮,MN組)與對照組(嗎啡+生理鹽水,MS組;生理鹽水+納洛酮,SN組),每組23只,采用連續(xù)6.5天嗎啡(10mg/kg,bid,IP)注射后進(jìn)行一次納洛酮催癮(0.3mg/kg,IP),同時搭配條件性位置訓(xùn)練箱建立CPA大鼠模型,從day7下午至day13上午,對CPA大鼠進(jìn)行每天2次的消退行為訓(xùn)練,第14天,對CPA行為消退了的大鼠進(jìn)行藥物“點燃”重建； 2、分別在套管針植入術(shù)后3-5天,CPA建立前、后及消退與重建后用微透析方法收集伏隔核殼區(qū)的細(xì)胞外液；采用高效液相色譜-電化學(xué)方法檢測透析液中DA及DOPAC濃度。 3、所有結(jié)果如非特殊說明,均以均數(shù)±標(biāo)準(zhǔn)誤(Mean±SEM)表示,多組均數(shù)間的多重比較,采用方差分析(ANOVA),組內(nèi)行為學(xué)和不同時間點神經(jīng)遞質(zhì)的兩兩比較采用Independent-Samples t-test。當(dāng)P0.05被認(rèn)為差異具有統(tǒng)計學(xué)意義。所有的統(tǒng)計分析均采用SPSS16.0軟件完成。 結(jié)果 1、連續(xù)6天半的嗎啡注射與納洛酮一次催癮搭配可以成功建立CPA模型,實驗鼠表現(xiàn)出明顯的厭惡動機(jī),對伴藥側(cè)表現(xiàn)出明顯的回避；經(jīng)過連續(xù)7天的消退訓(xùn)練后CPA行為可以成功消退；而消退后的CPA大鼠經(jīng)藥物“點燃”并納洛酮催癮后CPA行為可成功重建; 2、MN組大鼠伏隔核殼區(qū)多巴胺及DOPAC水平在CPA建立后明顯升高(P0.01),而MS組與SN組較建立前差異無統(tǒng)計學(xué)意義(P0.05)；經(jīng)過為期一周的消退訓(xùn)練之后,條件戒斷大鼠DA/DOPAC水平明顯下降至基礎(chǔ)水平;CPA行為重建后,MN組大鼠伏隔核殼區(qū)的DA/DOPAC水平明顯升高,與MS組、SN組相比差異具有顯著統(tǒng)計學(xué)意義(P0.01)。 結(jié)論 1、小劑量納洛酮可以誘發(fā)嗎啡依賴大鼠CPA的產(chǎn)生,經(jīng)過為期一周的無藥狀態(tài)下消退行為訓(xùn)練,CPA行為可以成功消退,當(dāng)再次暴露于藥物相關(guān)環(huán)境時,消退了的CPA行為可以重建; 2、伏隔核殼區(qū)的多巴胺與其代謝產(chǎn)物DOPAC可能參與小劑量納洛酮所誘發(fā)的嗎啡依賴大鼠的條件性位置厭惡,中腦邊緣系統(tǒng)的多巴胺機(jī)制可能在嗎啡依賴的厭惡動機(jī)方面起到十分重要的調(diào)節(jié)作用。
[Abstract]:Purpose. The changes of dopamine dopamine (dopamine) and its metabolite, 3O4 dihydroxyphenyl acetic acid3 (DOPAC) in the nucleus putamen region of nucleus accumbens in morphine dependent rats induced by naloxone were determined. To explore the neurobiochemical mechanism of morphine dependent negative enhancement. Method. 1Sixty-nine SPF male Sprage-Dawley rats were randomly divided into two groups: the experimental group (morphine naloxone MN group) and the control group (morphine saline group MS), and the saline naloxone SN group with 23 rats in each group. The rats of CPA were induced by naloxone injection of 10 mg / kg IP for 6.5 days after injection of naloxone (0.3 mg / kg). The model of CPA rats was established by matching the conditioned position training box. From the afternoon of day7 to the morning of day13, the rats of CPA were trained twice a day in regression behavior, and the rats were trained twice a day on the 14th day. The drug "kindling" was performed on the rats whose CPA behavior disappeared. 2. Extracellular fluids in the nucleus and shell of accumbens were collected by microdialysis before and after the establishment of CPA at 3-5 days after cannula implantation, and the concentrations of DA and DOPAC in dialysis solution were detected by high performance liquid chromatography (HPLC) and electrochemical method. 3. All results, if not specified, are expressed as mean 鹵standard error mean 鹵SEM, multiple comparisons between multiple groups of mean, ANOVAN was used to compare behavior and neurotransmitters at different time points with Independent-Samples t-test.When P0.05 was considered to be statistically significant, all statistical analyses were performed by SPSS16.0 software. Results. 1. Six and a half days of morphine injection combined with naloxone can successfully establish the CPA model. The experimental mice showed obvious aversion motivation and obvious avoidance to the side of the drug. After 7 days of continuous regression training, the CPA behavior could be successfully dissipated, while the subsided CPA rats could be successfully reconstructed after drug "kindling" and naloxone-induced CPA behavior. (2) the levels of dopamine and DOPAC in the nucleus putamen of accumbent septum of rats in MN group increased significantly after the establishment of CPA, but there was no significant difference between group MS and group SN before establishment, and after one week of regression training, there was no significant difference between MS group and SN group. The level of DA/DOPAC was significantly decreased to the basic level in conditioned abstinence rats. The level of DA/DOPAC in the nucleus putamen of the accumbent septum in MN group was significantly higher than that in the SN group of MS, and there was a significant difference between MN group and MS group (P 0.01). Conclusion. 1. Low dose naloxone could induce the production of CPA in morphine dependent rats. After a week's training of regression behavior in drug-free state, the behavior of CPA could be successfully dissipated, and the subsided CPA behavior could be reconstructed when exposed to drug-related environment again. 2. Dopamine in the nucleus and shell of accumbent septum and its metabolite DOPAC may be involved in the conditioned positional aversion of morphine dependent rats induced by low dose naloxone. The dopamine mechanism in the midbrain limbic system may play an important role in the aversion motivation of morphine dependence.
【學(xué)位授予單位】：新鄉(xiāng)醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R749.6

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本文編號：1685410