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研究生： 范欣怡
Fan, Hsin-Yi
論文名稱： 蛋白質合成抑制劑Anisomycin的處理可能破壞古柯鹼條件化情境記憶的提取與再凝固化歷程
Anisomycin Treatment may Disrupt Retrieval and Reconsolidation of the Cocaine-conditioned Contextual Memory
指導教授： 游一龍
Yu, Lung
學位類別： 碩士
Master
系所名稱： 醫學院 - 行為醫學研究所
Institute of Behavioral Medicine
論文出版年： 2009
畢業學年度： 97
語文別： 英文
論文頁數： 44
中文關鍵詞： 杏仁核 、情境記憶 、場地偏好 、提取 、再凝固化 、古柯鹼
外文關鍵詞： contextual memory, CPP, retrieval, amygdala, cocaine, anisomycin, reconsolidation
相關次數： 點閱：185  下載：2 
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    • 即使停用古柯鹼一段很長的時間，與古柯鹼相關的條件化情境仍對此種藥物的心理渴求及再度使用扮演了一個很重要的角色。若能將古柯鹼的條件化情境記憶消除，或許就能把它用來作為處理渴求及預防復發的策略之ㄧ。至今已有許多研究證據支持：記憶的再提取會使記憶處在一個不穩定的狀態，需要經歷一個蛋白質合成的過程方能再次穩定此記憶。本研究即利用兩種蛋白質合成抑制劑Anisomycin和Cycloheximide，以及不同的記憶活化方式，來檢驗及改變古柯鹼的條件化情境記憶。我們發現在提取記憶前若給予ㄧ劑Anisomycin，可短暫抑制古柯鹼條件化的場地偏好記憶，但不影響此記憶本質。另外，古柯鹼再凝固化的歷程只有在同時呈現古柯鹼和先前的條件化情境下，才能被Anisomycin或Cycloheximide破壞。僅給予古柯鹼但不再次經歷先前的情境，或單獨呈現先前的情境但不施予古柯鹼，皆無法有效改變古柯鹼條件化情境記憶的再凝固化歷程。此外，將Anisomycin注入基底側的杏仁核亦可得到類似的結果。綜合上述，我們認為古柯鹼條件化情境記憶的提取與再凝固化歷程需要蛋白質的合成，藥物及先前條件化情境的再經驗比其他處理方式更能活化此古柯鹼相關記憶，進而使此記憶更容易被破壞。

    Cocaine-conditioned context manifests as a pivotal factor in inducing cocaine craving and relapse even following an extensive abstinence. To extinguish cocaine-conditioned contextual memory, thus, may be used as a strategy in treating cocaine craving and relapse. To date, several lines of evidence support the notion that retrieval of memory renders the memory becoming a labile state, which in turn undergoes a protein synthesis-dependent process to restabilize the memory. This study aimed to examine the effect of anisomycin and cycloheximide, protein synthesis inhibitors, on ameliorating the cocaine-conditioned contextual memory when differing memory activation methods were used. We found that systemic anisomycin treatment prior to the retrieval test temporarily suppressed the cues-provoked cocaine conditioned place preference (CPP) memory, but did not affect the cocaine-associated memory per se. Besides, reconsolidation of the cocaine-conditioned contextual memory was disrupted by systemic anisomycin or cycloheximide treatment only in mice presented with both cocaine injection and the previously conditioned context. Nonetheless, anisomycin or cycloheximide treatment failed to alter reconsolidation of the cocaine-conditioned contextual memory in mice presented with the previously conditioned context alone or presented with cocaine alone. Furthermore, intra-nucleus injection of amsomycin into the basolateral amygdala obtained the similar results. Take together, we suggest that protein synthesis is necessary for retrieval and reconsolidation of the cocaine-conditioned contextual memory; meanwhile, concomitant re-experience of both drug and previously conditioned context is more effect than other treatment to reactivate the cocaine-associated memories and make it more susceptible to be abolished.

    中文摘要..................................................2 Abstract..................................................3 誌謝......................................................5 Contents..................................................7 List of figures and tables...............................10 1.Introduction...........................................12 2.Materials and methods..................................15 2.1.Animals..............................................15 2.2.Drugs and chemicals..................................15 2.3.Place preference apparatus...........................15 2.4.Stereotaxic Instruments and Surgery..................16 2.5.Procedures...........................................16 2.5-1.Basic procedure of CPP establishing and testing....17 2.5-2.Retrieval protocol.................................18 2.5-3.Reconsolidation protocol: CPP test as a reactivation trial....................................................18 2.5-3.1.One activation and anisomycin injection..........18 2.5-3.2.Two activations and anisomycin injections on separate days............................................18 2.5-3.3.One activation and two cycloheximide injections separated by 8 hrs.......................................19 2.5-4.Reconsolidation protocol: Re-pairing as a reactivation trial.......................................19 2.5-4.1.Re-paired with both cocaine-context and saline-context..................................................19 2.5-4.2.Re-paired with cocaine-context alone.............20 2.5-4.3.Re-experienced without any previous context......20 2.5-5.Summary of protocols and treatments in the study...21 2.6.Locomotor activity...................................21 2.7.Histology............................................22 2.8.Statistics...........................................22 3.Results................................................23 3.1.Systemic pretreatment of anisomycin temporarily suppressed retrieval of the cocaine-induced CPP, but did not affect the cocaine-associated memory per se..........23 3.2-1.Single systemic post-test injection of anisomycin did not affect reconsolidation of the cocaine-induced CPP......................................................23 3.2-2.Two systemic injections of anisomycin following the CPP tests on separate days did not affect reconsolidation of the cocaine-induced CPP as well.......................24 3.2-3.Mice received two cycloheximide injections separated by 8 hours after single activation of CPP test exhibited no difference with control group.........................24 3.3-1.An established cocaine-induced CPP did not become labile after the context recall, but required the concomitant re-experience of both drug and previously conditioned context......................................25 3.3-2.Cocaine re-pairing alone was not sufficient to destabilize the cocaine-associated memory................26 3.3-3.Cocaine-induced CPP did not be affected without re-experiencing any previously conditioned context..........26 3.4.Summary of the results in the study..................27 3.5.Anisomycin injection did not affect the locomotor activity.................................................27 4.Discussion.............................................28 5.Figures................................................31 6.References.............................................42

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