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題名 左旋茶胺酸對大鼠甲基安非他命制約場地偏好和自我給藥的影響
Effects of L-theanine on methamphetamine conditioned place preference and self-administration in rats
作者 鄭閔軒
Cheng, Min-Hsuan
貢獻者 詹銘煥
Chan, Ming-Huan
鄭閔軒
Cheng, Min-Hsuan
關鍵詞 甲基安非他命
左旋茶胺酸
制約場地偏好
自我給藥
再犯
Methamphetamine
L-theanine
Conditioned place preference
Self-administration
Reinstatement
日期 2022
上傳時間 1-Aug-2022 18:14:41 (UTC+8)
摘要 甲基安非他命藥物濫用是全球性的公共衛生問題。左旋茶胺酸是左旋麩胺酸和左旋麩醯胺酸的胺基酸類似物，過去被證明能調節不同腦區的麩胺酸、γ-胺基丁酸和多巴胺的水平。本研究採用甲基安非他命誘發的制約場地偏好(CPP)和甲基安非他命靜脈自我給藥(SA)模型，透過在這兩種實驗模型的不同階段給予左旋茶胺酸，釐清其對大鼠場地制約及操作制約的習得、表現、動機、消除及再犯的影響。實驗一.：左旋茶胺酸在制約場地偏好於每次進行甲基安非他命和環境制約前給予，及自我給藥固定比率(FR1)時程進行前急性給予，探討對制約場地偏好的習得和自我給藥的增強作用的影響。實驗二.：在進行制約場地偏好之制約後測驗前急性給予左旋茶胺酸，測試其對制約場地偏好行為表現的效果。實驗三.：左旋茶胺酸在自我給藥累進比率(PR)時程前急性給予，確定其對取得甲基安非他命的動機是否有所影響。實驗四.：左旋茶胺酸在再犯階段前急性給予，測試其對制約場地偏好和自我給藥相關行為再犯反應之影響。實驗五.：左旋茶胺酸在制約場地偏好中，重複性於每次消除實驗結束後給予，以確定其是否能促進消除階段完成及減少再犯行為。實驗六.：於制約場地偏好及自我給藥之制約習得後進行數日強制禁戒，並於期間每日給予左旋茶胺酸，評估對於後續消除以及再犯之影響。結果表明，左旋茶胺酸對甲基安非他命的制約場地偏好的習得、表現以及自我給藥增強作用及取得藥物動機並無影響。此外左旋茶胺酸急性給予，在兩種實驗模型中皆能有效減少再犯反應。再者，左旋茶胺酸於制約場地偏好實驗每次消除過程後給予及強制禁戒時給予皆有加強消除並減少再犯情形，但在自我給藥模型中強制禁戒時給予並無良好改善效果。並且左旋茶胺酸對食物制約場地偏好和甲基安非他命誘導的過度活動行為皆無影響。這些發現表明左旋茶胺酸可能具有抑制甲基安非他命成癮復發的潛力。
Methamphetamine (METH) abuse is a significant public health problem worldwide. L-theanine, an amino acid analog of L-glutamate and L-glutamine, has previously been shown to modulate levels of glutamate, GABA, and dopamine in various brain regions. The present study employed the conditioned place preference (CPP) and intravenous self-administration (IVSA) paradigm in Sprague-Dawley rats to investigate the effects of L-theanine on the acquisition, expression, motivation, extinction, and reinstatement of the place conditioning and operant conditioning involved in CPP and SA. L-theanine (3 or 10 mg/kg, ip) and vehicle were administered at the different sessions of these two experimental models. Experiment 1: L-theanine was given prior to each CPP conditioning session and acutely in the SA FR1 training schedule to determine its effect on the acquisition of CPP and SA. Experiment 2: L-theanine was administered before the post-conditioning test to examine its acute effect on CPP expression. Experiment 3: L-theanine was given acutely in the SA PR schedule to determine its effect on motivation to access METH. Experiment 4: L-theanine was administered before reinstatement to examine its acute effect on reinstatement of CPP and SA. Experiment 5: L-theanine was repeatedly administered after each extinction session to determine whether it can facilitate extinction memory and reduce reinstatement. Experiment 6: the effects of repeated administration of L-theanine during forced abstinence following extinction and reinstatement were assessed in both CPP and SA. The results demonstrated that L-theanine did not affect the acquisition and expression of METH-induced CPP nor affect the reinforcement and motivation of METH-induced SA. However, L-theanine significantly reduced the reinstatement acutely in both models. Moreover, L-theanine facilitated the extinction as well as reduced the reinstatement when given after each extinction session and during forced abstinence in CPP, while it didn’t ameliorate the related issues in SA. L-theanine also exhibited no effect on food CPP, and METH-induced locomotor hyperactivity. These findings suggested that L-theanine might have the anti-relapse potential for METH addiction.
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描述 碩士
國立政治大學
神經科學研究所
108754006
資料來源 http://thesis.lib.nccu.edu.tw/record/#G0108754006
資料類型 thesis
dc.contributor.advisor 詹銘煥zh_TW
dc.contributor.advisor Chan, Ming-Huanen_US
dc.contributor.author (Authors) 鄭閔軒zh_TW
dc.contributor.author (Authors) Cheng, Min-Hsuanen_US
dc.creator (作者) 鄭閔軒zh_TW
dc.creator (作者) Cheng, Min-Hsuanen_US
dc.date (日期) 2022en_US
dc.date.accessioned 1-Aug-2022 18:14:41 (UTC+8)-
dc.date.available 1-Aug-2022 18:14:41 (UTC+8)-
dc.date.issued (上傳時間) 1-Aug-2022 18:14:41 (UTC+8)-
dc.identifier (Other Identifiers) G0108754006en_US
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/141189-
dc.description (描述) 碩士zh_TW
dc.description (描述) 國立政治大學zh_TW
dc.description (描述) 神經科學研究所zh_TW
dc.description (描述) 108754006zh_TW
dc.description.abstract (摘要) 甲基安非他命藥物濫用是全球性的公共衛生問題。左旋茶胺酸是左旋麩胺酸和左旋麩醯胺酸的胺基酸類似物，過去被證明能調節不同腦區的麩胺酸、γ-胺基丁酸和多巴胺的水平。本研究採用甲基安非他命誘發的制約場地偏好(CPP)和甲基安非他命靜脈自我給藥(SA)模型，透過在這兩種實驗模型的不同階段給予左旋茶胺酸，釐清其對大鼠場地制約及操作制約的習得、表現、動機、消除及再犯的影響。實驗一.：左旋茶胺酸在制約場地偏好於每次進行甲基安非他命和環境制約前給予，及自我給藥固定比率(FR1)時程進行前急性給予，探討對制約場地偏好的習得和自我給藥的增強作用的影響。實驗二.：在進行制約場地偏好之制約後測驗前急性給予左旋茶胺酸，測試其對制約場地偏好行為表現的效果。實驗三.：左旋茶胺酸在自我給藥累進比率(PR)時程前急性給予，確定其對取得甲基安非他命的動機是否有所影響。實驗四.：左旋茶胺酸在再犯階段前急性給予，測試其對制約場地偏好和自我給藥相關行為再犯反應之影響。實驗五.：左旋茶胺酸在制約場地偏好中，重複性於每次消除實驗結束後給予，以確定其是否能促進消除階段完成及減少再犯行為。實驗六.：於制約場地偏好及自我給藥之制約習得後進行數日強制禁戒，並於期間每日給予左旋茶胺酸，評估對於後續消除以及再犯之影響。結果表明，左旋茶胺酸對甲基安非他命的制約場地偏好的習得、表現以及自我給藥增強作用及取得藥物動機並無影響。此外左旋茶胺酸急性給予，在兩種實驗模型中皆能有效減少再犯反應。再者，左旋茶胺酸於制約場地偏好實驗每次消除過程後給予及強制禁戒時給予皆有加強消除並減少再犯情形，但在自我給藥模型中強制禁戒時給予並無良好改善效果。並且左旋茶胺酸對食物制約場地偏好和甲基安非他命誘導的過度活動行為皆無影響。這些發現表明左旋茶胺酸可能具有抑制甲基安非他命成癮復發的潛力。zh_TW
dc.description.abstract (摘要) Methamphetamine (METH) abuse is a significant public health problem worldwide. L-theanine, an amino acid analog of L-glutamate and L-glutamine, has previously been shown to modulate levels of glutamate, GABA, and dopamine in various brain regions. The present study employed the conditioned place preference (CPP) and intravenous self-administration (IVSA) paradigm in Sprague-Dawley rats to investigate the effects of L-theanine on the acquisition, expression, motivation, extinction, and reinstatement of the place conditioning and operant conditioning involved in CPP and SA. L-theanine (3 or 10 mg/kg, ip) and vehicle were administered at the different sessions of these two experimental models. Experiment 1: L-theanine was given prior to each CPP conditioning session and acutely in the SA FR1 training schedule to determine its effect on the acquisition of CPP and SA. Experiment 2: L-theanine was administered before the post-conditioning test to examine its acute effect on CPP expression. Experiment 3: L-theanine was given acutely in the SA PR schedule to determine its effect on motivation to access METH. Experiment 4: L-theanine was administered before reinstatement to examine its acute effect on reinstatement of CPP and SA. Experiment 5: L-theanine was repeatedly administered after each extinction session to determine whether it can facilitate extinction memory and reduce reinstatement. Experiment 6: the effects of repeated administration of L-theanine during forced abstinence following extinction and reinstatement were assessed in both CPP and SA. The results demonstrated that L-theanine did not affect the acquisition and expression of METH-induced CPP nor affect the reinforcement and motivation of METH-induced SA. However, L-theanine significantly reduced the reinstatement acutely in both models. Moreover, L-theanine facilitated the extinction as well as reduced the reinstatement when given after each extinction session and during forced abstinence in CPP, while it didn’t ameliorate the related issues in SA. L-theanine also exhibited no effect on food CPP, and METH-induced locomotor hyperactivity. These findings suggested that L-theanine might have the anti-relapse potential for METH addiction.en_US
dc.description.tableofcontents 誌謝 I
摘要 III
Abstract IV
目錄 VI
圖表目錄 VIII
縮寫對照表 X
壹、 緒論 1
一、 甲基安非他命 (methamphetamine) 1
二、 成癮 5
三、 左旋茶胺酸 (L-theanine) 13
貳、 實驗假說 19
參、 研究動機與實驗目的 20
肆、 研究目標 21
伍、 實驗材料與方法 22
一、 實驗動物 22
二、 實驗藥品製備 22
三、 實驗方法及流程 25
四、 實驗數據分析 34
陸、 實驗結果 36
一、 制約場地偏好實驗 (conditioned place preference) 36
二、 自我給藥實驗 (self-administration) 41
三、 運動活性測試 (locomotor activity) 47
柒、 討論 49
捌、 結論 55
玖、 參考文獻 56
壹拾、 圖表 65		zh_TW
dc.format.extent 2610137 bytes-
dc.format.mimetype application/pdf-
dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G0108754006en_US
dc.subject (關鍵詞) 甲基安非他命zh_TW
dc.subject (關鍵詞) 左旋茶胺酸zh_TW
dc.subject (關鍵詞) 制約場地偏好zh_TW
dc.subject (關鍵詞) 自我給藥zh_TW
dc.subject (關鍵詞) 再犯zh_TW
dc.subject (關鍵詞) Methamphetamineen_US
dc.subject (關鍵詞) L-theanineen_US
dc.subject (關鍵詞) Conditioned place preferenceen_US
dc.subject (關鍵詞) Self-administrationen_US
dc.subject (關鍵詞) Reinstatementen_US
dc.title (題名) 左旋茶胺酸對大鼠甲基安非他命制約場地偏好和自我給藥的影響zh_TW
dc.title (題名) Effects of L-theanine on methamphetamine conditioned place preference and self-administration in ratsen_US
dc.type (資料類型) thesisen_US
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dc.identifier.doi (DOI) 10.6814/NCCU202200897en_US