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題名 抑制外側韁核對大鼠場地制約的影響效果
Effects of inactivation of the lateral habenula on place conditioning in rats作者 楊季樺
Yang, Chi-Hua貢獻者 廖瑞銘<br>趙知章
楊季樺
Yang, Chi-Hua關鍵詞 場地制約偏好
疆核
GABA受體致效劑
心理興奮劑
Conditioned place preference
Habenula
GABA receptor agonist
Psychostimulant日期 2018 上傳時間 20-Jul-2018 18:04:58 (UTC+8) 摘要 個體面對不同的外部刺激選擇合宜的行為反應，同時對環境的變化具備行為調整與學習之能力有助於生物體的存活。中腦邊緣多巴胺系統在上述行為中扮演重要的角色，其涉及個體的酬賞動機與聯結學習等認知行為。根據神經解剖學與行為神經科學的研究，外側韁核可以調控中腦邊緣多巴胺系統進而影響酬賞相關的動機行為；迄今絕大多數研究是使用操作式制約行為作業檢測外側韁核的神經活動與酬賞相關行為的關係，較少研究探討抑制外側韁核對於多巴胺相關之古典式制約行為的影響。因此本研究透過藥理抑制的方式，探討外側韁核的GABA受體對於場地制約行為的影響。實驗一的結果顯示GABAa受體致效劑muscimol注入外側韁核無法引發場地制約偏好(CPP)。實驗二的結果同時將muscimol及GABAb受體致效劑baclofen混合液(B/M)注入外側韁核無法形成CPP，惟有增加藥物制約配對箱的自發性活動量。實驗三進行周邊注射安非它命(d-AMP)0.5, 1, 2 mg/kg的劑量反應，發現其無法令受試習得CPP，但有增加藥物配對箱的行為活動量。實驗四進行B/M注入外側韁核結合腹腔注射d-AMP，其可有效地使受試習得CPP。綜合上述的實驗結果顯示，單獨以GABA類受體致效劑抑制外側韁核或以較低劑量的d-AMP周邊注射，皆無法讓個體形成顯著的CPP，而須在這兩項藥物處置同時進行方得顯著的CPP，這意含抑制外側韁核可以增強個體對於藥物酬賞相關的古典式制約學習行為。
The ability of appropriate reaction to different kinds of external stimuli as well as behavioral flexibility in cases of response reinforcement contingencies being changed are essential for survival. Such behaviors involved in reward motivation and associative learning are known to be mediated by the mesolimbic dopamine (DA) systems. In terms of anatomy and behavioral neuroscience, the lateral habenula (LHb) has been suggested to modulate reward-related behaviors that are mediated by the mesolimbic DA systems. While there have been a number of studies using operant conditioning task to Investigate the role of the LHb in reward-related behavior, less work has attended on the role of the LHb in reward-related behavior as measured by the tasks based on classical conditioning theory. Therefore, in the present study, we investigated the effects of inactivation of the LHb by using GABA agonists on place conditioning task. The results of Experiment 1 show that intra-LHb infusion of muscimol, a GABAa agonist, did not produce any significant place conditioning. The results of Experiment 2 show that a mixture of the GABAb and GABAa agonists, baclofen and muscimol (B/M), infused into the LHb did not establish any significant place conditioning; even with the enhanced locomotor activity observed in drug-paired chamber during the conditioning sessions. In Experiment 3, we examined the dose effects of d-amphetamine (d-AMP; 0, 0.5, 1, or 2 mg/kg; IP) on place conditioning, and there was no drug-induced conditioned place preference (CPP). Locomotor activity was enhanced by d-AMP in drug-paired chamber during the conditioning session. The results of Experiment 4 show that intra-LHb infusion of B/M combined with IP injection of d-AMP significantly induced CPP. These data demonstrated that neither intra-LHb infusion of GABA agonists alone nor systemic injection of d-AMP alone produced significant place conditioning, but a CPP was developed by two aforementioned drug treatments administered in combination. Thus, the inactivation of the LHb is indicated to facilitate the individual in acquiring task involved classical conditioning of drug reward to contextual cue.參考文獻 Akirav I, Raizel H, Maroun M (2006) Enhancement of conditioned fear extinction by infusion of the GABA(A) agonist muscimol into the rat prefrontal cortex and amygdala. Eur J Neurosci 23:758-764.Baker PM, Jhou T, Li B, Matsumoto M, Mizumori SJY, Stephenson-Jones M, Vicentic A (2016) The lateral habenula circuitry: reward processing and cognitive control. J Neurosci 36:11482-11488.Baker PM, Raynor SA, Francis NT, Mizumori SJY (2017) Lateral habenula integration of proactive and retroactive information mediates behavioral flexibility. 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國立政治大學
神經科學研究所
103754010資料來源 http://thesis.lib.nccu.edu.tw/record/#G1037540101 資料類型 thesis dc.contributor.advisor 廖瑞銘<br>趙知章 zh_TW dc.contributor.author (Authors) 楊季樺 zh_TW dc.contributor.author (Authors) Yang, Chi-Hua en_US dc.creator (作者) 楊季樺 zh_TW dc.creator (作者) Yang, Chi-Hua en_US dc.date (日期) 2018 en_US dc.date.accessioned 20-Jul-2018 18:04:58 (UTC+8) - dc.date.available 20-Jul-2018 18:04:58 (UTC+8) - dc.date.issued (上傳時間) 20-Jul-2018 18:04:58 (UTC+8) - dc.identifier (Other Identifiers) G1037540101 en_US dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/118785 - 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) 103754010 zh_TW dc.description.abstract (摘要) 個體面對不同的外部刺激選擇合宜的行為反應，同時對環境的變化具備行為調整與學習之能力有助於生物體的存活。中腦邊緣多巴胺系統在上述行為中扮演重要的角色，其涉及個體的酬賞動機與聯結學習等認知行為。根據神經解剖學與行為神經科學的研究，外側韁核可以調控中腦邊緣多巴胺系統進而影響酬賞相關的動機行為；迄今絕大多數研究是使用操作式制約行為作業檢測外側韁核的神經活動與酬賞相關行為的關係，較少研究探討抑制外側韁核對於多巴胺相關之古典式制約行為的影響。因此本研究透過藥理抑制的方式，探討外側韁核的GABA受體對於場地制約行為的影響。實驗一的結果顯示GABAa受體致效劑muscimol注入外側韁核無法引發場地制約偏好(CPP)。實驗二的結果同時將muscimol及GABAb受體致效劑baclofen混合液(B/M)注入外側韁核無法形成CPP，惟有增加藥物制約配對箱的自發性活動量。實驗三進行周邊注射安非它命(d-AMP)0.5, 1, 2 mg/kg的劑量反應，發現其無法令受試習得CPP，但有增加藥物配對箱的行為活動量。實驗四進行B/M注入外側韁核結合腹腔注射d-AMP，其可有效地使受試習得CPP。綜合上述的實驗結果顯示，單獨以GABA類受體致效劑抑制外側韁核或以較低劑量的d-AMP周邊注射，皆無法讓個體形成顯著的CPP，而須在這兩項藥物處置同時進行方得顯著的CPP，這意含抑制外側韁核可以增強個體對於藥物酬賞相關的古典式制約學習行為。 zh_TW dc.description.abstract (摘要) The ability of appropriate reaction to different kinds of external stimuli as well as behavioral flexibility in cases of response reinforcement contingencies being changed are essential for survival. Such behaviors involved in reward motivation and associative learning are known to be mediated by the mesolimbic dopamine (DA) systems. In terms of anatomy and behavioral neuroscience, the lateral habenula (LHb) has been suggested to modulate reward-related behaviors that are mediated by the mesolimbic DA systems. While there have been a number of studies using operant conditioning task to Investigate the role of the LHb in reward-related behavior, less work has attended on the role of the LHb in reward-related behavior as measured by the tasks based on classical conditioning theory. Therefore, in the present study, we investigated the effects of inactivation of the LHb by using GABA agonists on place conditioning task. The results of Experiment 1 show that intra-LHb infusion of muscimol, a GABAa agonist, did not produce any significant place conditioning. The results of Experiment 2 show that a mixture of the GABAb and GABAa agonists, baclofen and muscimol (B/M), infused into the LHb did not establish any significant place conditioning; even with the enhanced locomotor activity observed in drug-paired chamber during the conditioning sessions. In Experiment 3, we examined the dose effects of d-amphetamine (d-AMP; 0, 0.5, 1, or 2 mg/kg; IP) on place conditioning, and there was no drug-induced conditioned place preference (CPP). Locomotor activity was enhanced by d-AMP in drug-paired chamber during the conditioning session. The results of Experiment 4 show that intra-LHb infusion of B/M combined with IP injection of d-AMP significantly induced CPP. These data demonstrated that neither intra-LHb infusion of GABA agonists alone nor systemic injection of d-AMP alone produced significant place conditioning, but a CPP was developed by two aforementioned drug treatments administered in combination. Thus, the inactivation of the LHb is indicated to facilitate the individual in acquiring task involved classical conditioning of drug reward to contextual cue. en_US dc.description.tableofcontents 中文摘要 ------------------------------------------------- I英文摘要 ------------------------------------------------ II目錄 --------------------------------------------------- IV圖次 --------------------------------------------------- VI第一章、緒論 --------------------------------------------- 1一. 前言 ------------------------------------------------ 1二. 多巴胺系統 ------------------------------------------- 1三. 韁核 ------------------------------------------------ 2四. 外側韁核神經元 --------------------------------------- 3五. 外側韁核與酬賞相關行為 -------------------------------- 5六. 場地制約作業 ----------------------------------------- 8七. 研究目的與實驗設計 ------------------------------------ 9第二章、實驗材料與方法 ----------------------------------- 11一、 受試者 -------------------------------------------- 11二、 場地制約作業的測試儀器 ------------------------------ 11三、 腦部埋管手術 --------------------------------------- 11四、 藥物 --------------------------------------------- 12五、 顱內注射藥物 -------------------------------------- 12六、 場地制約作業的訓練程序 ------------------------------ 13七、 實驗步驟 ------------------------------------------ 14八、 組織學檢驗 ---------------------------------------- 15九、 統計分析 ------------------------------------------ 16第三章、結果 ----------------------------------------- 18一、 組織學檢驗 -------------------------------------- 18二、 實驗一：MUS微量注射至外側韁核在場地制約作業的結果 ----- 18三、 實驗二：B/M微量注射至外側韁核在場地制約作業的結果 ----- 19四、 實驗三：周邊注射D-AMP在場地制約作業的結果 ------------ 19五、 實驗四：抑制外側韁核對周邊注射D-AMP在場地制約作業的影響 -20第四章、討論 ------------------------------------------- 23一、 GABA類受體致效劑注入外側韁核在場地制約作業的探討 ------ 23二、 周邊注射D-AMP在場地制約作業的探討 -------------------- 27三、 B/M注入外側韁核結合腹腔注射D-AMP在場地制約作業的探討 -- 28四、 外側韁核與多巴胺神經元 ---------------------------- 29五、 未來研究方向 ------------------------------------ 30六、 結論 ------------------------------------------- 31參考文獻 ------------------------------------------- 32附圖 ---------------------------------------------- 41附錄目次 ------------------------------------------- 55附錄表一 ------------------------------------------- 56附錄圖一至七 ---------------------------------------- 57 zh_TW dc.format.extent 3516817 bytes - dc.format.mimetype application/pdf - dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G1037540101 en_US dc.subject (關鍵詞) 場地制約偏好 zh_TW dc.subject (關鍵詞) 疆核 zh_TW dc.subject (關鍵詞) GABA受體致效劑 zh_TW dc.subject (關鍵詞) 心理興奮劑 zh_TW dc.subject (關鍵詞) Conditioned place preference en_US dc.subject (關鍵詞) Habenula en_US dc.subject (關鍵詞) GABA receptor agonist en_US dc.subject (關鍵詞) Psychostimulant en_US dc.title (題名) 抑制外側韁核對大鼠場地制約的影響效果 zh_TW dc.title (題名) Effects of inactivation of the lateral habenula on place conditioning in rats en_US dc.type (資料類型) thesis en_US dc.relation.reference (參考文獻) Akirav I, Raizel H, Maroun M (2006) Enhancement of conditioned fear extinction by infusion of the GABA(A) agonist muscimol into the rat prefrontal cortex and amygdala. 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