本文關(guān)鍵詞： 芋螺毒素類似物 nNOS 嗎啡 條件性位置偏愛 獎賞效應(yīng)　出處：《浙江大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：1.目的 在實驗室前期研究的基礎(chǔ)上,驗證芋螺毒素類似物[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])抗嗎啡精神依賴的作用,觀察嗎啡成癮小鼠海馬腦區(qū)nNOS表達(dá)水平的變化,探討其在嗎啡成癮過程中可能的作用機制,為進(jìn)一步設(shè)計、篩選抗嗎啡依賴的芋螺毒素類似物提供理論和實驗依據(jù)。 2.實驗方法 采用清潔級雄性昆明種小鼠,用CPP模型檢測嗎啡成癮小鼠行為學(xué)改變,用Western blotting檢測目標(biāo)蛋白變化。 3.結(jié)果 CPP實驗結(jié)果表明,單次側(cè)腦室注射120、240、480、960pmol Glu-Con-G,120、240、480pmol Glu-Con-G[1-11]和480、960pmol Glu-Con-G[S16Y]可以抑制嗎啡誘導(dǎo)小鼠的CPP表達(dá)和復(fù)燃,且所給劑量均不影響小鼠的運動活性和探索行為。 Western blotting實驗結(jié)果顯示,一定劑量的Glu-Con-G、Glu-Con-G [1-11]、Glu-Con-G[S16Y]可以抑制嗎啡成癮小鼠海馬腦區(qū)n N O S表達(dá)的增加。 4.結(jié)論 1.側(cè)腦室注射單次給予120、240、480、960pmol Glu-Con-G,120.240、480pmol Glu-Con-G[1-11]和480、960pmol Glu-Con-G[S16Y]可抑制嗎啡誘導(dǎo)小鼠的CPP的表達(dá)和復(fù)燃； 2.所給劑量的三種芋螺毒素類似物,在CPP建立和復(fù)燃階段,可以抑制長期嗎啡處理引起的成癮小鼠海馬腦區(qū)n N0S蛋白含量的增加； 3.所給劑量均不影響小鼠的運動活性和探索行為； 4.Glu-Con-G[1-11]藥效較優(yōu),值得進(jìn)一步成藥性研究。
[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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R994

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本文編號：1504259