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題名 衝動反應的個別差異之神經基礎：DRL操作式制約行為與藥物酬賞行為的相關
Neural basis of individual differences of impulsive action：correlation between DRL operant behavior and drug-reward behavior
作者 莊淳聿
貢獻者 廖瑞銘
莊淳聿
關鍵詞 藥物成癮
安非他命
多巴胺
制約性場地偏好
低頻反應區分增強作業
西方點墨
Drug addiction
Amphetamine
Dopamine
Conditioned place preference
Differential reinforcement of low-rates responding
Western blot
日期 2018
上傳時間 23-Jul-2018 16:51:38 (UTC+8)
摘要 不當的衝動反應已被認為與數種精神疾患有關(包含藥癮)，多元面向的衝動反應可區分為衝動選擇及衝動反應。針對衝動反應的個別差異與藥癮之間的關聯，本研究利用區辨性增強低頻反應作業(簡稱DRL作業)之行為表現的個別差異，在兩種安非他命引發的不同藥物酬賞行為［制約性場地偏好(簡稱CPP)與行為致敏化(簡稱BS)］，探討其相關性。行為藥理實驗後藉由西方點墨法，分析中腦多巴胺系統的五個相關腦區之四種蛋白質的含量：第一型多巴胺受體(dopamine D1 receptor)、第二型多巴胺受體(dopamine D2 receptor)、多巴胺轉運蛋白(dopamine transporter；DAT)及腦源性神經營養因子(brain-derived neurotrophic factor；BDNF)。實驗結果發現每一批48隻大鼠(共三批)，經14或17天的DRL行為訓練，其行為反應效率比值排序可以經四分位數，區分出高中低三群不等程度的衝動反應；這三群受試在六項DRL行為反應指標，均有顯著組間差異。實驗1的結果顯示，三組不同衝動程度的受試皆有顯著的CPP，惟DRL行為反應之個別差異與安非他命引發的CPP藥物酬賞效果並無統計相關。實驗1的生化分析顯示安非他命會對四種蛋白質在五個腦區有不同形式的影響效果，但其與DRL行為反應並無任何統計相關。實驗2的結果顯示DRL行為反應之個別差異與安非他命誘發BS的效果有顯著相關，即DRL行為反應效率較好的低衝動組受試，其藥物引發BS行為反應效果較弱；反之亦然。實驗2的生化分析結果顯示，背側紋狀體的D1受器與DRL行為個別差異之表現有正相關，背側紋狀體與海馬迴的DAT與安非他命引發BS藥效結果有正相關。綜合以上實驗結果，DRL行為反應所代表的衝動反應之個別差異，對於安非他命引發之CPP行為並無預測效果，但對於安非他命引發的BS有預測效果；而且這兩項藥物酬賞行為分別與不同腦區的多巴胺相關蛋白有獨特的統計相關，顯示DRL行為的個別差異之多巴胺相關神經基礎，取決於藥物酬賞行為的檢測模式。
Impulsive behavior has been considered to be related to several mental disorders including drug addiction. Individuals with abnormally high level of impulsivity are usually more likely to have drug addiction. This study used a differential reinforcement of low-rate response (DRL) task to investigate impulsive action that could be related to conditioned place preference (CPP) and behavioral sensitization (BS) as induced by amphetamine. Western blotting was used to analyze four proteins, dopamine D1 and D2 receptors, dopamine transporter (DAT) and brain-derived neurotrophic factor (BDNF), expressed in five brain regions relevant to the midbrain dopamine systems after psychopharmacological test. The results show that the subjects (n=47 or 48) in each of three batches trained in a DRL 10-sec task for 14 (or 17), based on the response efficiency, can be sorted by a quartile method into three groups with different levels of impulsivity (i.e., high, intermediate and low). The between-group difference was also confirmed on each of six measures of the present DRL behavior. Data of Experiment 1-1 and Experiment 1-2 together showed significant CPP induced by amphetamine; however, it was not correlated to the individual differences of DRL behavior. Biochemical assay of Experiment 1-2 revealed that amphetamine had different effects on the four proteins in the five brain regions, but these effects were not statistically correlated with behavioral responses of DRL. The results of Experiment 2 showed that the individual differences of DRL behavior were significantly correlated to the effects of amphetamine-induced BS. The low impulsive subjects had a weaker drug-induced BS and vice versa. Biochemical assay of Experiment 2 showed that there was a positive correlation between the amount of D1 receptors expressed in the dorsal striatum and the efficiency of DRL behavior; and in the dorsal striatum and the hippocampus, there was a positive correlation between the DAT and the BS induced by amphetamine. Together, the individual differences of impulse action assessed by DRL behavior can be used to predict the varied magnitudes of BS, but not CPP, induced by amphetamine. And, distinctive neural substrates are involved in psychopharmacological effects of CPP and BS induced by amphetamine.
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描述 碩士
國立政治大學
神經科學研究所 
104754001
資料來源 http://thesis.lib.nccu.edu.tw/record/#G0104754001
資料類型 thesis
dc.contributor.advisor 廖瑞銘zh_TW
dc.contributor.author (Authors) 莊淳聿zh_TW
dc.creator (作者) 莊淳聿zh_TW
dc.date (日期) 2018en_US
dc.date.accessioned 23-Jul-2018 16:51:38 (UTC+8)-
dc.date.available 23-Jul-2018 16:51:38 (UTC+8)-
dc.date.issued (上傳時間) 23-Jul-2018 16:51:38 (UTC+8)-
dc.identifier (Other Identifiers) G0104754001en_US
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/118809-
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) 104754001zh_TW
dc.description.abstract (摘要) 不當的衝動反應已被認為與數種精神疾患有關(包含藥癮)，多元面向的衝動反應可區分為衝動選擇及衝動反應。針對衝動反應的個別差異與藥癮之間的關聯，本研究利用區辨性增強低頻反應作業(簡稱DRL作業)之行為表現的個別差異，在兩種安非他命引發的不同藥物酬賞行為［制約性場地偏好(簡稱CPP)與行為致敏化(簡稱BS)］，探討其相關性。行為藥理實驗後藉由西方點墨法，分析中腦多巴胺系統的五個相關腦區之四種蛋白質的含量：第一型多巴胺受體(dopamine D1 receptor)、第二型多巴胺受體(dopamine D2 receptor)、多巴胺轉運蛋白(dopamine transporter；DAT)及腦源性神經營養因子(brain-derived neurotrophic factor；BDNF)。實驗結果發現每一批48隻大鼠(共三批)，經14或17天的DRL行為訓練，其行為反應效率比值排序可以經四分位數，區分出高中低三群不等程度的衝動反應；這三群受試在六項DRL行為反應指標，均有顯著組間差異。實驗1的結果顯示，三組不同衝動程度的受試皆有顯著的CPP，惟DRL行為反應之個別差異與安非他命引發的CPP藥物酬賞效果並無統計相關。實驗1的生化分析顯示安非他命會對四種蛋白質在五個腦區有不同形式的影響效果，但其與DRL行為反應並無任何統計相關。實驗2的結果顯示DRL行為反應之個別差異與安非他命誘發BS的效果有顯著相關，即DRL行為反應效率較好的低衝動組受試，其藥物引發BS行為反應效果較弱；反之亦然。實驗2的生化分析結果顯示，背側紋狀體的D1受器與DRL行為個別差異之表現有正相關，背側紋狀體與海馬迴的DAT與安非他命引發BS藥效結果有正相關。綜合以上實驗結果，DRL行為反應所代表的衝動反應之個別差異，對於安非他命引發之CPP行為並無預測效果，但對於安非他命引發的BS有預測效果；而且這兩項藥物酬賞行為分別與不同腦區的多巴胺相關蛋白有獨特的統計相關，顯示DRL行為的個別差異之多巴胺相關神經基礎，取決於藥物酬賞行為的檢測模式。zh_TW
dc.description.abstract (摘要) Impulsive behavior has been considered to be related to several mental disorders including drug addiction. Individuals with abnormally high level of impulsivity are usually more likely to have drug addiction. This study used a differential reinforcement of low-rate response (DRL) task to investigate impulsive action that could be related to conditioned place preference (CPP) and behavioral sensitization (BS) as induced by amphetamine. Western blotting was used to analyze four proteins, dopamine D1 and D2 receptors, dopamine transporter (DAT) and brain-derived neurotrophic factor (BDNF), expressed in five brain regions relevant to the midbrain dopamine systems after psychopharmacological test. The results show that the subjects (n=47 or 48) in each of three batches trained in a DRL 10-sec task for 14 (or 17), based on the response efficiency, can be sorted by a quartile method into three groups with different levels of impulsivity (i.e., high, intermediate and low). The between-group difference was also confirmed on each of six measures of the present DRL behavior. Data of Experiment 1-1 and Experiment 1-2 together showed significant CPP induced by amphetamine; however, it was not correlated to the individual differences of DRL behavior. Biochemical assay of Experiment 1-2 revealed that amphetamine had different effects on the four proteins in the five brain regions, but these effects were not statistically correlated with behavioral responses of DRL. The results of Experiment 2 showed that the individual differences of DRL behavior were significantly correlated to the effects of amphetamine-induced BS. The low impulsive subjects had a weaker drug-induced BS and vice versa. Biochemical assay of Experiment 2 showed that there was a positive correlation between the amount of D1 receptors expressed in the dorsal striatum and the efficiency of DRL behavior; and in the dorsal striatum and the hippocampus, there was a positive correlation between the DAT and the BS induced by amphetamine. Together, the individual differences of impulse action assessed by DRL behavior can be used to predict the varied magnitudes of BS, but not CPP, induced by amphetamine. And, distinctive neural substrates are involved in psychopharmacological effects of CPP and BS induced by amphetamine.en_US
dc.description.tableofcontents 摘要 i
Abstract ii
目次 iv
附圖目次 vi
附錄圖 viii
附錄表 ix
第一章. 緒 論 1
一、 前言 1
二、 衝動與藥物濫用的關係 1
三、 衝動特質的剖析 1
四、 衝動與藥物上癮的實證研究 3
五、 藥物上癮與衝動特質的神經基礎 4
六、 制約性場地偏好與行為致敏化的比較 5
七、 個別差異 8
八、 研究目的 9
第二章. 材料與方法 11
一、 受試者 11
二、 實驗儀器 11
1. 操作式制約箱 11
2. 場地制約箱 12
3. 自發性行為活動測試儀器 12
三、 使用藥物 12
四、 行為作業的基本實驗步驟 13
1. 低頻反應區分增強作業 (DRL) 13
2. 制約性場地偏好 (conditioned place preference ; CPP) 14
3. 行為致敏化 (behavioral sensitization ; BS) 15
五、 生化分析 16
六、 統計方法 19
第三章. 實驗1：DRL-10行為差異與藥物引發制約性場地偏好 20
一、 目的 20
二、 實驗1-1步驟 20
三、 實驗1-1結果 21
四、 實驗1-1討論 24
五、 實驗1-2步驟 25
六、 實驗1-2結果 25
七、 實驗1-2討論 30
第四章. 實驗2：DRL-10行為差異與藥物引發行為致敏化 32
一、 目的 32
二、 實驗2步驟 32
三、 實驗2結果 32
四、 實驗2討論 36
第五章. 綜合討論 38
一、 DRL-10作業表現之個別差異與常態分佈 38
二、 藥癮行為結果與衝動群差異 40
三、 生化分析結果及其與行為實驗的相關分析 44
四、 結論 47
參考文獻 48
附圖 55
附錄圖 80
附錄表 85

 
附圖目次
Fig. 1：實驗1-1的受試在DRL-10作業14天習得歷程的效率、分佈狀況，與受試三分組後的DRL-10作業的習得的效率 55
Fig. 2：實驗1-1 DRL-10訓練第14天，不同衝動反應的三組受試之IRT曲線圖 56
Fig. 3：實驗1-1 受試分三群組後的總壓桿數、得酬賞之反應次數、未得酬賞之反應次數、促發反應次數、高峰時間、高峰頻率之結果 57
Fig. 4：實驗1-1 DRL-10兩次再測試的結果 58
Fig. 5：實驗1-1之首次CPP測試結果 59
Fig. 6：實驗1-1 CPP再燃測試與先前CPP的前後測相較之結果 60
Fig. 7：實驗1-1使用西方點墨分析實驗組與控制組，五個腦區中四種蛋白質的含量結果之比較 61
Fig. 8：實驗1-2的受試在DRL-10作業17天習得歷程的效率、分佈狀況，與受試三分組後的DRL-10作業的習得的效率 62
Fig. 9：實驗1-2 DRL-10訓練第17天，不同衝動反應的三組受試之IRT曲線圖 63
Fig. 10：實驗1-2 受試分三群組後的總壓桿數、得酬賞之反應次數、未得酬賞之反應次數、促發反應次數、高峰時間、高峰頻率之結果 64
Fig. 11：實驗1-2兩次 DRL-20 shift test的結果 65
Fig. 12：實驗1-2之首次CPP測試結果 66
Fig. 13：實驗1-2 CPP再燃測試與先前CPP的前後測相較之結果 67
Fig. 14：實驗1-2受試犧牲取腦前之活動量測試 68
Fig. 15：實驗1-2使用西方點墨分析實驗組與控制組，五個腦區中四種蛋白質的含量結果之比較 69
Fig. 16：實驗1-2安非他命處理受試的DRL-10效率與蛋白質含量的散佈圖結果 70
Fig. 17：實驗1-2安非他命處理受試的CPP後測結果與蛋白質含量的散佈圖結果 71
Fig. 18：實驗2的受試在DRL-10作業14天習得歷程的效率、分佈狀況，與受試三分組後的DRL-10作業的習得的效率 72
Fig. 19：實驗2 DRL-10訓練第14天，不同衝動反應的三組受試之IRT曲線圖 73
Fig. 20：實驗2受試分三群組後的總壓桿數、得酬賞之反應次數、未得酬賞之反應次數、促發反應次數、高峰時間、高峰頻率之結果 74
Fig. 21：實驗2 所有47隻受試的行為致敏化實驗結果 75
Fig. 22：實驗2行為致敏化實驗，受試分成高中低衝動三組的前後測活動量比較圖 76
Fig. 23：實驗2 DRL-10再測試與安非他命劑量反應測試 77
Fig. 24：實驗2 DRL行為效率與安非他命行為致敏化結果的散佈圖 78
Fig. 25：實驗2受試的DRL及藥癮行為表現與蛋白質含量的散佈圖 79
 
附錄圖
A-fig. 1：實驗1與實驗2受試的FR訓練結果 81
A-fig. 2：實驗1與實驗2受試的MRE及latency的結果 82
A-fig. 3：Exp.1-2 Elevated T-maze 83
A-fig. 4：Exp. 2 U型相關(2次函數散佈圖) 84
 
附錄表
A-Table 1：(Exp.1-1實驗組皮爾森相關係數表) 86
A-Table 2：(Exp.1-1控制組皮爾森相關係數表) 87
A-Table 4：(Exp.1-2實驗組皮爾森相關係數表) 88
A-Table 5：(Exp.1-2實驗組皮爾森相關係數表 – 刪去離群值) 89
A-Table 6：(Exp.1-2控制組皮爾森相關係數表) 90
A-Table 7：(Exp. 2皮爾森相關係數表) 91		zh_TW
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dc.format.mimetype application/pdf-
dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G0104754001en_US
dc.subject (關鍵詞) 藥物成癮zh_TW
dc.subject (關鍵詞) 安非他命zh_TW
dc.subject (關鍵詞) 多巴胺zh_TW
dc.subject (關鍵詞) 制約性場地偏好zh_TW
dc.subject (關鍵詞) 低頻反應區分增強作業zh_TW
dc.subject (關鍵詞) 西方點墨zh_TW
dc.subject (關鍵詞) Drug addictionen_US
dc.subject (關鍵詞) Amphetamineen_US
dc.subject (關鍵詞) Dopamineen_US
dc.subject (關鍵詞) Conditioned place preferenceen_US
dc.subject (關鍵詞) Differential reinforcement of low-rates respondingen_US
dc.subject (關鍵詞) Western bloten_US
dc.title (題名) 衝動反應的個別差異之神經基礎：DRL操作式制約行為與藥物酬賞行為的相關zh_TW
dc.title (題名) Neural basis of individual differences of impulsive action：correlation between DRL operant behavior and drug-reward behavioren_US
dc.type (資料類型) thesisen_US
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dc.identifier.doi (DOI) 10.6814/THE.NCCU.IN.002.2018.C05-