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研究生:連文宏
研究生(外文):Wen-Hung Lien
論文名稱:Cycloheximide對甲基安非他命所引發之場地制約偏好獲得與消褪的影響
論文名稱(外文):Effects of cycloheximide on the acquisition and extinction of methamphetamine-associated place preference
指導教授:游一龍游一龍引用關係
指導教授(外文):Lung Yu
學位類別:碩士
校院名稱:國立成功大學
系所名稱:行為醫學研究所
學門:社會及行為科學學門
學類:心理學類
論文種類:學術論文
論文出版年:2003
畢業學年度:91
語文別:英文
論文頁數:52
中文關鍵詞:蛋白質合成消褪場地制約偏好獲得記憶甲基安非他命
外文關鍵詞:acquisitionmethamphetamineconditioned place preferenceextinctionmemoryprotein synthesiscycloheximide
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本研究目的在於探討一種蛋白質合成抑制劑(cycloheximide)對甲基安非他命所建立的制約場地偏好(conditioned place preference,簡稱CPP)之獲得與消退所造成的影響。使用甲基安非他命每公斤體重二毫克的劑量對老鼠建立CPP後,該CPP透過每天重複的測試仍可維持一段相當長久的時間,甚至可以超過五十天之久。文獻指出有二種實驗策略可以讓甲基安非他命所建立起來的CPP加以消褪,一為每天重複測試,另一為強迫式消褪訓練。我們發現,利用上述任何一種消褪策略之前經過cycloheximide前處理的老鼠,相對於生理食鹽水前處理的老鼠已經展現CPP的消褪,該群老鼠仍維持CPP,尚未消褪,此一研究結果指出,甲基安非他命建立起CPP後的消褪須牽涉到蛋白質的合成。但有趣的是,經由cycloheximide前處理的老鼠似乎無法有效地阻斷或減弱甲基安非他命造成CPP的獲得。
從上述實驗中,我們得到三個結論:(一)甲基安非他命所建立起來的CPP可以維持相當長久的一段時間,而且利用每天重複測試,將老鼠暴露在當初用藥物制約的環境中,不再給予藥物,CPP仍很難加以消褪;(二)甲基安非他命所建立CPP的消褪需要新蛋白質的合成;(三)甲基安非他命CPP的獲得是否牽涉到蛋白質的合成須進一步的研究才能確立。
This study investigated the role of a protein synthesis inhibitor, cycloheximide, in the acquisition and extinction of methamphetamine (MA)-induced conditioned place preference (CPP). I demonstrated that the maintenance of the rapidly-established MA (2 mg/kg, ip)-associated CPP could be long-lasting and over fifty days, whereas the fluctuation was evident throughout the extinction process of repeated daily retention tests. Most importantly, cycloheximide-pretreated mice maintained the established MA-induced CPP and did not exhibit extinction of MA-associated CPP as compared to the saline-pretreated mice when they underwent a similar protocol of repeated daily retention tests or a forced extinction training. These results indicate that the protein synthesis is involved in the extinction of MA-induced CPP. Interestingly, cycloheximide-pretreated mice did not seem to exhibit attenuated acquisition of MA-associated CPP. I conclude that (1) MA-induced CPP could be maintained in a long-term manner and such CPP is reluctant to extinguish even animals'' repeated exposure to the previous conditioning environment at a drug-free status, (2) the extinction of MA-induced CPP requires a protein synthetic process and (3) the involvement of protein synthesis in the acquisition of MA-indeuced CPP seems to be indeterminate and requires further investigations.
1.Introduction....................................1
2.Materials and Methods...........................4
2.1. Subjects...................................4
2.2. Apparatus..................................5
2.2.1. Conditioned place preference apparatus5
2.2.2. Locomotor activity apparatus..........6
2.3. Experimental protocols.....................7
2.3.1. Experimental protocols utilizing
repeated daily retention tests as an
extinction strategy..... ............7
2.3.2. Experimental protocols utilizing the
forced extinction training as an
extinction strategy...................8
2.4. Experiments...............................10
2.4.1. Experiment 1: The exploratory test for
naive mice in the CPP apparatus......10
2.4.2. Experiment 2: Maintenance of the
MA-associated CPP....................11
2.4.3. Experiment 3A and B: Effects of
cycloheximide on the extinction of
MA-associated CPP by repeated daily
retention tests......................11
2.4.4. Experiment 4: Effects of cycloheximide
on the extinction of
MA-associated CPP by the forced
extinction training..................12
2.4.5. Experiment 5A and B: Effects of
cycloheximide on the spontaneous
locomotor activity...................13
2.4.6. Experiment 6: Effects of cycloheximide
on the acquisition of
MA-associated CPP....................14
2.5. Drugs.....................................15
2.6. Statistical analyses......................15
3. Results.......................................16
3.1. Experiment 1: Naive mice did not exhibit
preference bias between two end
compartments in our CPP apparatus..........16
3.2. Experiment 2: MA-associated CPP maintain
unaltered over a long period in
the repeated daily retention tests........16
3.3. Experiment 3A and B: The blocking effects of
cycloheximide on the
extinction of MA-associated CPP in the
repeated daily retention tests............17
3.4. Experiment 4: The blocking effects of
cycloheximide on the extinction of
MA-associated CPP in the forced extinction
training..................................19
3.5. Experiment 5A and B: There were no effects
of cycloheximide on the
locomotor activities within five days.....20
3.6. Experiment 6: Cycloheximide seemed to have
no effects on the acquisition
of MA-associated CPP......................21
4. Discussion....................................22
4.1. Extinction................................23
4.2. Acquisition...............................25
4.3. Maintenance...............................37
References.......................................36
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