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題名 麩胺酸對心理興奮劑引發制約性場地偏好行為之探討
The effects of glutamate on psychostimulant induced conditioned place preference
作者 張雅惠
Chang, Yea-Heuy
貢獻者 廖瑞銘
Liao, Ray-Ming
張雅惠
Chang, Yea-Heuy
關鍵詞 制約性場地偏好
古柯鹼
阿控博核
安非他命
麩胺酸
CPP
Cocaine
Accumbens
Amphetamine
Glutamate
日期 1997
上傳時間 18-Sep-2009 18:32:23 (UTC+8)
摘要 安非他命與古柯鹼皆屬心理興奮性藥物(psychostimulants),在藥理上有很多功能相似的機制,而且兩種藥物濫用成癮的問題一直是臨床及基礎研究所關心的問題。就動物行為模式而言,安非他命與古柯鹼具有影響包括反射性及制約學習性的行為表現的效果。若針對藥物的酬賞性做探討時,制約性場地偏好行為模式的相關研究益發受到重視,本研究實驗一先針對此作業之操弄時間及環境變項做一探討,再研究安非他命與古柯鹼之作用機制。過去的研究發現,週邊注射安非他命或古柯鹼與某環境刺激配對能引發制約性引發場地偏好的傾向,但兩藥的行為現象卻對藥理的操弄呈不一致的結果,隱含兩藥背後的神經機制可能也不同。其中阿控博核是一個值得再驗證的區域。阿控博核被認為是動機系統與運動系統的介面。此部位因其解剖及生化功能的異質性,故實驗二針對其次分區進行中樞藥物注射,於是直接將安非他命(10,15μg)與古柯鹼(50,100μg)分別注射於阿控博核之次級區。結果發現安非他命直接注入阿控博核核區或古柯鹼注入阿控博核殼區可表現顯著的場地偏好效果。基於阿控博核所含有的麩胺酸神經末梢源自內側前額葉皮質,實驗三則發現安非他命或古柯鹼注入內側前額葉皮質可引發制約性場地偏好行為。實驗四將麩胺酸專屬受體抑制劑與安非他命共同注入核區或與古柯鹼共同注入殼區,結果發現不論NMDA或non-NMDA受體抑制劑均減抑了安非他命與古柯鹼注入阿控博核不同區所引發之制約性場地偏好的效果。最後實驗五利用內側前額葉遭破壞的受試,發現古柯鹼注入阿控博核殼區所引發之制約性場地偏好的效果受損,但不影響安非他命注入阿控博核核區所引發之制約性場地偏好的效果。綜觀上述結果顯示安非他命與古柯鹼的酬賞特質所引發行為的神經機制可能不同,腦中之內側前額葉皮質及阿控博核對兩藥的行為效果有不同的涉入。
The function of the nucleus accumbens (NACC) has been suggestedto play an important role of the rewarding effects of psychostimulants.It is hypothesized that the neural substrates for amphetamine and cocaineto produce behavioral effects can be different. As conducted in Experiment 1, a conditioned place preference (CPP) task with procedures for amphetamine microinjection was established from the manipulation of conditioning environment. In considering the heterogeneity of NACC, Experiments 2 investigated the potentiality of the CPP effects after local infusion of amphetamine (10, 15 μg/site) or cocaine (50, 100 μg/site) into the core and shell subareas of NACC. Amphetamine microinjection into the NACC core significantly produced CPP, whereas such effect only appeared under treatment of the high dose of cocaine into the shell area. Lack of the CPP effects for amphetamine or cocaine infused into the boundary areas of the core and shell regions was seen in Experiment 2 (part B). In Experiment 3, the involvement of the medial prefrontal cortex (mPFC) was challenged for amphetamine and cocaine on the CPP task. Both doses of cocaine and the low dose of amphetamine locally infused in mPFC significantly produced CPP. In Experiment 4, glutamatergic NMDA receptor antagonist APV (0.5, 1 μg/site) and non-NMDA receptor antagonist CNQX (1 μg/site) significantly attenuated the CPP effects of amphetamine infused into the NACC core. This antagonism was also true for the cocaine-induced CPP in the NACC shell. These results implied that the other cortical areas can modulate such CPP effects, in particular the mPFC. In Eperiment 5, lesion of mPFC significantly inhibited the cocaine-induced CPP in the shell area but not for the amphetamine-induced CPP in the core area. Taken together, the NACC is an important neural substrate for mediating the rewarding effects for amphetamine and cocaine on the CPP task, and such effects can be dissociated as drugs locally infused into core and shell areas. Glutamatergic projections originating mPFC may provide some motivational information to the NACC. The mPFC may distinctly be involved in the motive circuit of cocaine- or amphetamine-induced CPP in the NACC. These results highlight that different processes are involved in the acquisition of CPP for microinjection of amphetamine or cocaine into the NACC subareas.
描述 碩士
國立政治大學
心理學研究所
84752006
86
資料來源 http://thesis.lib.nccu.edu.tw/record/#B2002001748
資料類型 thesis
dc.contributor.advisor 廖瑞銘zh_TW
dc.contributor.advisor Liao, Ray-Mingen_US
dc.contributor.author (Authors) 張雅惠zh_TW
dc.contributor.author (Authors) Chang, Yea-Heuyen_US
dc.creator (作者) 張雅惠zh_TW
dc.creator (作者) Chang, Yea-Heuyen_US
dc.date (日期) 1997en_US
dc.date.accessioned 18-Sep-2009 18:32:23 (UTC+8)-
dc.date.available 18-Sep-2009 18:32:23 (UTC+8)-
dc.date.issued (上傳時間) 18-Sep-2009 18:32:23 (UTC+8)-
dc.identifier (Other Identifiers) B2002001748en_US
dc.identifier.uri (URI) https://nccur.lib.nccu.edu.tw/handle/140.119/36429-
dc.description (描述) 碩士zh_TW
dc.description (描述) 國立政治大學zh_TW
dc.description (描述) 心理學研究所zh_TW
dc.description (描述) 84752006zh_TW
dc.description (描述) 86zh_TW
dc.description.abstract (摘要) 安非他命與古柯鹼皆屬心理興奮性藥物(psychostimulants),在藥理上有很多功能相似的機制,而且兩種藥物濫用成癮的問題一直是臨床及基礎研究所關心的問題。就動物行為模式而言,安非他命與古柯鹼具有影響包括反射性及制約學習性的行為表現的效果。若針對藥物的酬賞性做探討時,制約性場地偏好行為模式的相關研究益發受到重視,本研究實驗一先針對此作業之操弄時間及環境變項做一探討,再研究安非他命與古柯鹼之作用機制。過去的研究發現,週邊注射安非他命或古柯鹼與某環境刺激配對能引發制約性引發場地偏好的傾向,但兩藥的行為現象卻對藥理的操弄呈不一致的結果,隱含兩藥背後的神經機制可能也不同。其中阿控博核是一個值得再驗證的區域。阿控博核被認為是動機系統與運動系統的介面。此部位因其解剖及生化功能的異質性,故實驗二針對其次分區進行中樞藥物注射,於是直接將安非他命(10,15μg)與古柯鹼(50,100μg)分別注射於阿控博核之次級區。結果發現安非他命直接注入阿控博核核區或古柯鹼注入阿控博核殼區可表現顯著的場地偏好效果。基於阿控博核所含有的麩胺酸神經末梢源自內側前額葉皮質,實驗三則發現安非他命或古柯鹼注入內側前額葉皮質可引發制約性場地偏好行為。實驗四將麩胺酸專屬受體抑制劑與安非他命共同注入核區或與古柯鹼共同注入殼區,結果發現不論NMDA或non-NMDA受體抑制劑均減抑了安非他命與古柯鹼注入阿控博核不同區所引發之制約性場地偏好的效果。最後實驗五利用內側前額葉遭破壞的受試,發現古柯鹼注入阿控博核殼區所引發之制約性場地偏好的效果受損,但不影響安非他命注入阿控博核核區所引發之制約性場地偏好的效果。綜觀上述結果顯示安非他命與古柯鹼的酬賞特質所引發行為的神經機制可能不同,腦中之內側前額葉皮質及阿控博核對兩藥的行為效果有不同的涉入。zh_TW
dc.description.abstract (摘要) The function of the nucleus accumbens (NACC) has been suggestedto play an important role of the rewarding effects of psychostimulants.It is hypothesized that the neural substrates for amphetamine and cocaineto produce behavioral effects can be different. As conducted in Experiment 1, a conditioned place preference (CPP) task with procedures for amphetamine microinjection was established from the manipulation of conditioning environment. In considering the heterogeneity of NACC, Experiments 2 investigated the potentiality of the CPP effects after local infusion of amphetamine (10, 15 μg/site) or cocaine (50, 100 μg/site) into the core and shell subareas of NACC. Amphetamine microinjection into the NACC core significantly produced CPP, whereas such effect only appeared under treatment of the high dose of cocaine into the shell area. Lack of the CPP effects for amphetamine or cocaine infused into the boundary areas of the core and shell regions was seen in Experiment 2 (part B). In Experiment 3, the involvement of the medial prefrontal cortex (mPFC) was challenged for amphetamine and cocaine on the CPP task. Both doses of cocaine and the low dose of amphetamine locally infused in mPFC significantly produced CPP. In Experiment 4, glutamatergic NMDA receptor antagonist APV (0.5, 1 μg/site) and non-NMDA receptor antagonist CNQX (1 μg/site) significantly attenuated the CPP effects of amphetamine infused into the NACC core. This antagonism was also true for the cocaine-induced CPP in the NACC shell. These results implied that the other cortical areas can modulate such CPP effects, in particular the mPFC. In Eperiment 5, lesion of mPFC significantly inhibited the cocaine-induced CPP in the shell area but not for the amphetamine-induced CPP in the core area. Taken together, the NACC is an important neural substrate for mediating the rewarding effects for amphetamine and cocaine on the CPP task, and such effects can be dissociated as drugs locally infused into core and shell areas. Glutamatergic projections originating mPFC may provide some motivational information to the NACC. The mPFC may distinctly be involved in the motive circuit of cocaine- or amphetamine-induced CPP in the NACC. These results highlight that different processes are involved in the acquisition of CPP for microinjection of amphetamine or cocaine into the NACC subareas.en_US
dc.description.tableofcontents 目次
     附錄圖表說明
     中文摘要 1
     英文摘要 2
     壹、緒論 3
     一、心理興奮劑------------------------------------------------------------------4
     二、制約性場地偏好--------------------------------------------------------------7
     三、阿控博核與內側前額葉皮質----------------------------------------------------11
     四、麩胺酸----------------------------------------------------------------------14
     研究目的------------------------------------------------------------------------17
     
     貳、研窕方法--------------------------------------------------------------------20
      受試者------------------------------------------------------------------------20
      儀器--------------------------------------------------------------------------20
      手術--------------------------------------------------------------------------20
      顱內注射藥物------------------------------------------------------------------21
      制約性場地偏好程序------------------------------------------------------------21
      組織切片----------------------------------------------------------------------22
      統計分析----------------------------------------------------------------------23
     
     參、實驗一:制約性場地偏好作業之探討--------------------------------------------24
     肆、實驗二:安非他命與古柯鹼在阿控博核核區及殼區形成制約性場地偏好的效果--------27
     伍、實驗三:心理興奮劑於內側前額葉引發制約性場地偏好行為之探討------------------30
     陸、實驗四:麩胺酸對心理興奮劑引發制約性場地偏好行為之探討----------------------33
     柒、實驗五:內側前額葉皮質--阿控博核網路之探討----------------------------------36
     捌、綜合討論--------------------------------------------------------------------38
     
     參考文獻------------------------------------------------------------------------41
     
     附錄圖表------------------------------------------------------------------------54
     
     附錄圖表說明
     表一 實驗二A部份的統計結果---------------------------------------------------------------------------------------------------54
     表二 實驗四部份的統計結果----------------------------------------------------------------------------------------------------55
     表三 實驗三部份的統計結果----------------------------------------------------------------------------------------------------56
     圖一 內側前額葉與阿控博核之突觸聯會圖----------------------------------------------------------------------------------------57
     圖二 內側前額葉與阿控博核之神經網路圖----------------------------------------------------------------------------------------58
     圖三 環境刺激對安非他命引發制約性場地偏好行為之影響--------------------------------------------------------------------------59
     圖四 安非他命引發制約性場地偏好行為的時間變化--------------------------------------------------------------------------------60
     圖五 安非他命微量注射入阿控博核引發之自發性活動量變化------------------------------------------------------------------------61
     圖六 藥物微量注射入阿控博核核區(上圖)及殼區(下圖)之組織學檢驗結果--------------------------------------------------------62
     圖七 藥物微量注射入阿控博核核區與殼區邊界(上圖)及後側般區(下圖)之組織學檢驗結果------------------------------------------63
     圖八 安非他命與古柯鹼微量注射入阿控博核引發之制約性場地偏好行為效果----------------------------------------------------------64
     圖九 安非他命與古柯鹼微量注射入阿控博核核區與殼區邊界及後側殼區引發之制約性場地偏好行為效果----------------------------------65
     圖十 藥物微量注射入內側前額葉皮質前扣帶區/前邊緣區(上圖)及下邊緣區(下圖)之組織學檢驗結果--------------------------------66
     圖十一 安非他命與古柯鹼微量注射入內側前額葉皮質前扣帶區/前邊緣區(上圖)及下邊緣區(下圖)引發之制約性場地偏好行為效果------67
     圖十二 安非他命微量注射入阿控博核核區與麩胺酸亞型受體抑制劑對制約性場地偏好行為之影響效果------------------------------------68
     圖十三 古柯鹼微量注射入阿控博核殼區與麩胺酸亞型受體抑制劑對制約性場地偏好行為之影響效果--------------------------------------69
     圖十四 內側前額紮皮質破壞後之組織學檢驗結果----------------------------------------------------------------------------------70
     圖十五 內側前額葉皮質破壞後對安非他命微量注入阿控博核核區及古柯鹼微量注入殼區引發制約性場地偏好行為之影響效果----------------71
zh_TW
dc.language.iso en_US-
dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#B2002001748en_US
dc.subject (關鍵詞) 制約性場地偏好zh_TW
dc.subject (關鍵詞) 古柯鹼zh_TW
dc.subject (關鍵詞) 阿控博核zh_TW
dc.subject (關鍵詞) 安非他命zh_TW
dc.subject (關鍵詞) 麩胺酸zh_TW
dc.subject (關鍵詞) CPPen_US
dc.subject (關鍵詞) Cocaineen_US
dc.subject (關鍵詞) Accumbensen_US
dc.subject (關鍵詞) Amphetamineen_US
dc.subject (關鍵詞) Glutamateen_US
dc.title (題名) 麩胺酸對心理興奮劑引發制約性場地偏好行為之探討zh_TW
dc.title (題名) The effects of glutamate on psychostimulant induced conditioned place preferenceen_US
dc.type (資料類型) thesisen