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    Please use this identifier to cite or link to this item: https://nccur.lib.nccu.edu.tw/handle/140.119/55303


    Title: 以制約場地偏好行為模式探討藥癮復發的行為神經機制 (II)
    Other Titles: Investigation of Neurobehavioral Mechanisms of Drug Relapse by the Use of Conditioned Place Preference Model
    Authors: 廖瑞銘
    Contributors: 國立政治大學心理學系
    行政院國家科學委員會
    Keywords: 藥物酬賞;藥物（癮）再復發;制約式場地偏好行為;大腦多巴胺系統
    drug reward;drug reinstatement;conditioned place preference;brain dopamine systems
    Date: 2009
    Issue Date: 2012-11-08 14:05:16 (UTC+8)
    Abstract: Accumulative evidence supports the idea that the addicted drugs act as reinforcers of drug-taking and drug-seeking behaviors. From the past, it is argued that the mesolimbic dopamine (DA) systems play a major role of the underlying neural mechanisms for drug reward. The dopaminergic mechanisms mediating the drug reward and/or addiction are more complicated than what were thought in the past. There is a bottleneck to reveal the behavioral mechanisms for a sophisticated delineation of drug addiction. Despite the aforementioned progress made on in psychopharmacology of drug reward, it is still not clear about the underlying neural mechanisms for drug reinstatement also known as the relapse in clinic. Therefore, this 2-year project investigated the neurobehavioral mechanisms of drug reinstatement with a focus of using amphetamine CPP model in the rat. In the first year, the major work was to establish an animal behavior model of drug reinstatement in amphetamine conditioned place preference. With several experiments, the extinction protocol was verified to work, that consisted of 4 cycles of 2 days (exposure to CPP context without any injection in one day and CPP re-testing in the other day) and followed by a 3-day withdrawal (staying in home cage). In the second year, experiments with pharmacological manipulations will be conducted to study the neural substrates for the drug reinstatement on aforementioned place conditioned behavior. A dose dependent effect of amphetamine to prime the extinguished CPP was obtained based on the aforementioned extinction protocol. Regarding the role of dopamine subtype receptors involved in drug reinstatement, D1, but not D2, receptor agonist reactivates amphetamine CPP. Furthermore, preliminary data show such effect is mediated by brain-derived neurotrophic factor (BDNF) expression ih the medial prefrontal cortex. Together, the current data provide a further step in revealing the neurobehavioral mechanisms underlying drug reward and reinstatement of amphetamine. Throughout executing this project, one SCI paper publication and at least five conferences paper presentations have been completed among other relevant academic accreditations obtained.
    越來越多的證據顯示上癮的藥物對「嗑藥」與「求藥」行為扮演增強物的角色，過去的研究證據顯示大腦多巴胺系統對這種藥物酬賞行為的增強扮演重要的角色。最近的研究持續的關注多巴胺與藥物酬賞之間的關係，主要的評論認為大腦多巴胺不應只是產生酬賞增強作用而已。行為層面的探討就如同神經機制的探討一樣，目前都有待突破瓶頸。行為層面的重要課題之一，便是有關停用藥物一段時日後的再復發現象。本項二年期專題研究計畫預計執行實驗內容是：第一年建立以安非他命引發制約性場地偏好行為之再復發的動物模式；第二年對此再復發行為進行藥理的操弄測試。實驗結果首先在於確認一個有效的「消除」步驟，其包括四個兩天的週期（含第一天放入CPP 兩側配對箱與第二天的CPP 再測，均無任何注射），及三天留滯在各自的飼養籠。利用這項步驟將所習得的CPP 消除，再用較低的安非它命劑量引燃CPP 的效果，實驗結果得到顯著的藥物反應劑量。這項安非它命的引燃CPP 效果，可以被多巴胺D1（而不是D2）的致效劑取代。另外，安非它命CPP 的再犯行為與前額葉皮質的大腦神經滋養因子（BDNF）的表現有關。這個計劃的成果進一步的解析安非它命藥物復發行為的神經機制，執行過程中的學術論著發表包括一篇SCI 期刊論文及至少五篇的國際會議論文，同時還有一些其它間接的學術成果。
    Relation: 基礎研究
    學術補助
    研究期間:9708~ 9907
    研究經費:1167仟元
    Data Type: report
    Appears in Collections:[Department of Psychology] NSC Projects

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