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系統識別號 U0026-1408201415515600
論文名稱(中文) 大麻素一號受體拮抗劑利莫那班對於古柯鹼相關記憶的穩固化、再穩固化以及消除歷程之影響
論文名稱(英文) Effects of the cannabinoid CB1 receptor antagonist rimonabant on consolidation, reconsolidation, and forced extinction of cocaine-associated memory
校院名稱 成功大學
系所名稱(中) 心理學系認知科學碩士班
系所名稱(英) MS in Cognitive Science
學年度 102
學期 2
出版年 103
研究生(中文) 劉亞薇
研究生(英文) Ya-Wei Liu
學號 U76014041
學位類別 碩士
語文別 英文
論文頁數 54頁
口試委員 口試委員-梁庚辰
口試委員-游一龍
指導教授-胡書榕
口試委員-陳德祐
中文關鍵字 古柯鹼  復發  大麻素一號受體  利莫那班  穩固化歷程  再穩固化歷程  消除歷程  制約場地偏好 
英文關鍵字 Cocaine  Relapse  Cannabinoid CB1 receptor  Rimonabant  Consolidation  Reconsolidation  Forced extinction  Conditioned place preference 
學科別分類
中文摘要 古柯鹼濫用在當今社會中是一個相當嚴重的問題,截至目前為止尚未找到有效防止古柯鹼復發的方式。另一方面我們體內的內生性大麻素系統目前已知可以調控包含古柯鹼在內的多種成癮藥物的酬賞效果,但是唯獨針對古柯鹼的濫用,大麻素一號受體並未參與在古柯鹼的主要酬賞效果中,而是參與了古柯鹼復發的歷程。因此本研究旨在利用古柯鹼誘發制約場地偏好的動物模型來探討大麻素一號受體拮抗劑利莫那班是否參與在古柯鹼相關記憶的穩固化、再穩固化以及消除歷程。我們的實驗結果發現,以系統性或是於內側前額葉皮質注射利莫那班阻斷大麻素一號受體,對於古柯鹼相關記憶的穩固化會有雙向的調節。當以低劑量古柯鹼來誘發場地制約偏好時,大麻素一號受體的阻斷會促進該記憶的穩固化;當以高劑量古柯鹼誘發場地制約偏好,則相同處置會損害該記憶的穩固化。此外,以利莫那班阻斷大麻素一號受體會損壞古柯鹼相關記憶的再穩固化歷程以及促進古柯鹼相關記憶的消除歷程。綜合上述結果,大麻素一號受體的阻斷可以在臨床上用以促進高劑量古柯鹼成癮者對該藥物記憶的消除歷程,進而避免古柯鹼的復發。
英文摘要 Relapse to cocaine has been an unsolved problem for decades. The endocannabinoid system modulates addiction of several abused drugs including cocaine. The cannabinoid CB1 receptors have previously been implicated in the reinstatement but not the primary rewarding effect of cocaine. The purpose of this study was to exam whether rimonabant, a cannabinoid CB1 receptor antagonist, affected consolidation, reconsolidation and forced extinction of cocaine-associated memory by using a conditioned place preference (CPP) paradigm. Our results revealed that the CB1 receptors bidirectionally modulate cocaine-associated memory. That is, inactivation of CB1 receptors, either peripherally or within the medial prefrontal cortex (mPFC), facilitates memory consolidation of cocaine-induced CPP at low doses, whereas disrupts that at high ones. Rimonabant was also found to impair reconsolidation but dose-dependently facilitate forced extinction of cocaine-associated memory. Taken together, pharmacological targeting CB1 receptors may be a therapeutic strategy to prevent from relapse to cocaine in cocaine heavy users.
論文目次 摘要.....2
Abstract.....3
Introduction.....8
Materials and Methods.....14
1. Animal Models and Administration.....14
2. Drugs.....14
3. Cocaine-induced conditioned place preference (CPP).....14
4. Stereotaxic surgery.....16
5. Intra-mPFC infusion.....17
6. Rimonabant CPA/CPP test.....17
7. Locomotor activity.....18
8. Histology.....18
9. Experimental design.....19
10. Statistical analysis.....22
Results.....23
Discussion.....28
References.....36
Figures.....41

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