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題名 慢性疼痛或壓力情境對於類鴉片delta受體的調節與其抗憂鬱功能的改變
Effects of chronic pain or stress on the modulation of delta opioid receptor and its mediated antidepressant-like effect作者 陳昶名 貢獻者 柯美全
陳昶名關鍵詞 憂鬱症
發炎性疼痛
長期壓力
類鴉片delta受體
制效劑
depression
inflammatory pain
chronic stress
delta opioid receptor
agonist日期 2009 上傳時間 8-Dec-2010 11:40:34 (UTC+8) 摘要 憂鬱症是盛行的精神疾病之一。慢性疼痛或是處在長期壓力情境的患者常與憂鬱症產生共病。在動物研究中，類鴉片delta受體制效劑能產生抗憂鬱效果，並且在發炎性疼痛的研究也指出類鴉片delta受體制效劑能展現抗痛覺過敏的效果。本研究主要利用大白鼠腦室內給予類鴉片delta受體制效劑SNC80以及三環抗憂鬱劑amitriptyline，來探討並比較其所產生的抗憂鬱效果在發炎性疼痛或長期壓力情境下與正常情境下的異同。大白鼠強迫游泳試驗被用來比較測試藥物的抗憂鬱效果；佛氏完全佐劑經由皮下注射至大白鼠右後腳掌底板來產生發炎性疼痛；腎上腺皮質酮經由皮下注射且持續21天來產生長期性壓力；西方墨點法用來檢驗在發炎性疼痛或長期壓力下，類鴉片delta受體蛋白質在大白鼠海馬迴的細胞膜上的改變。另外，拮抗劑實驗則用來確認類鴉片delta受體所產生的抗憂鬱效果。實驗結果顯示，大白鼠在正常情境下，SNC80及amitriptyline皆能產生抗憂鬱效果；然而在發炎性疼痛下，SNC80所產生的抗憂鬱效果有提高的表現，並且類鴉片delta受體蛋白質的數量在海馬迴的細胞膜上也隨著疼痛的時間增長而增加，amitriptyline則跟正常情境下的效果相似。另外，大白鼠在長期性壓力下，SNC80的抗憂鬱效果則沒有提高的表現，並且類鴉片delta受體蛋白質的數量在海馬迴的細胞膜上也未受到改變。本研究透過行為實驗提出類鴉片delta受體制效劑的藥理特性，並用分子生物學的方法來對應行為實驗的結果。本研究可做為未來類鴉片delta受體制效劑在治療慢性疼痛的憂鬱症患者上，可能發展為抗憂鬱藥的一個證據。
Depression is one of the most prevalent mental illnesses all over the world. Patients with chronic pain or stress often have depression. Previous studies have shown that delta opioid receptor (DOR) agonists produced antidepressant-like effects in animal models and that antihyperalgesic effects of DOR agonists can be enhanced in rats under inflammatory pain. The aim of the study was to investigate and compare the antidepressant-like effects of a DOR agonist, SNC80, and a tricyclic antidepressant, amitriptyline, following intracerebroventricular (i.c.v.) administration in rats under different states. The forced swim test was used to determine the antidepressant-like effects of test compounds. Complete Freund’s adjuvant was injected subcutaneously into the right hind paw of rats to elicit inflammatory pain. Corticosterone was injected subcutaneously once per day for 21 days to induce chronic stress. The western blot was used to quantify the levels of DOR protein on plasma membrane in the hippocampus of rats under inflammatory pain or chronic stress. In addition, antagonist experiment was conducted to verify the receptor mechanism underlying the antidepressant-like effects of DOR agonist. Results indicated that i.c.v. SNC80 and amitriptyline dose-dependently produced antidepressant-like effects in rats under normal state. More importantly, the potency of SNC80-induced antidepressant-like effects, but not amitriptyline, was enhanced in rats under inflammatory pain. In addition, up-regulation of supraspinal DORs was time-dependently associated with enhanced antidepressant-like effects of SNC80 in rats under inflammatory pain. On the other hand, SNC80 did not produce enhanced antidepressant-like effects, and DOR density was not changed in rats under chronic stress. This study provides evidence of the DOR agonist’s state-dependent effects and suggests that DOR agonists may be more effective as potential antidepressants for patients with depression comorbid with chronic pain.參考文獻 Adachi, M., Barrot, M., Autry, A. E., Theobald, D., & Monteggia, L. M. (2008). Selective loss of brain-derived neurotrophic factor in the dentate gyrus attenuates antidepressant efficacy. Biological Psychiatry, 63(7), 642-649.
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國立政治大學
心理學研究所
96752003
98資料來源 http://thesis.lib.nccu.edu.tw/record/#G0096752003 資料類型 thesis dc.contributor.advisor 柯美全 zh_TW dc.contributor.author (Authors) 陳昶名 zh_TW dc.creator (作者) 陳昶名 zh_TW dc.date (日期) 2009 en_US dc.date.accessioned 8-Dec-2010 11:40:34 (UTC+8) - dc.date.available 8-Dec-2010 11:40:34 (UTC+8) - dc.date.issued (上傳時間) 8-Dec-2010 11:40:34 (UTC+8) - dc.identifier (Other Identifiers) G0096752003 en_US dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/49446 - 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) 96752003 zh_TW dc.description (描述) 98 zh_TW dc.description.abstract (摘要) 憂鬱症是盛行的精神疾病之一。慢性疼痛或是處在長期壓力情境的患者常與憂鬱症產生共病。在動物研究中，類鴉片delta受體制效劑能產生抗憂鬱效果，並且在發炎性疼痛的研究也指出類鴉片delta受體制效劑能展現抗痛覺過敏的效果。本研究主要利用大白鼠腦室內給予類鴉片delta受體制效劑SNC80以及三環抗憂鬱劑amitriptyline，來探討並比較其所產生的抗憂鬱效果在發炎性疼痛或長期壓力情境下與正常情境下的異同。大白鼠強迫游泳試驗被用來比較測試藥物的抗憂鬱效果；佛氏完全佐劑經由皮下注射至大白鼠右後腳掌底板來產生發炎性疼痛；腎上腺皮質酮經由皮下注射且持續21天來產生長期性壓力；西方墨點法用來檢驗在發炎性疼痛或長期壓力下，類鴉片delta受體蛋白質在大白鼠海馬迴的細胞膜上的改變。另外，拮抗劑實驗則用來確認類鴉片delta受體所產生的抗憂鬱效果。實驗結果顯示，大白鼠在正常情境下，SNC80及amitriptyline皆能產生抗憂鬱效果；然而在發炎性疼痛下，SNC80所產生的抗憂鬱效果有提高的表現，並且類鴉片delta受體蛋白質的數量在海馬迴的細胞膜上也隨著疼痛的時間增長而增加，amitriptyline則跟正常情境下的效果相似。另外，大白鼠在長期性壓力下，SNC80的抗憂鬱效果則沒有提高的表現，並且類鴉片delta受體蛋白質的數量在海馬迴的細胞膜上也未受到改變。本研究透過行為實驗提出類鴉片delta受體制效劑的藥理特性，並用分子生物學的方法來對應行為實驗的結果。本研究可做為未來類鴉片delta受體制效劑在治療慢性疼痛的憂鬱症患者上，可能發展為抗憂鬱藥的一個證據。 zh_TW dc.description.abstract (摘要) Depression is one of the most prevalent mental illnesses all over the world. Patients with chronic pain or stress often have depression. Previous studies have shown that delta opioid receptor (DOR) agonists produced antidepressant-like effects in animal models and that antihyperalgesic effects of DOR agonists can be enhanced in rats under inflammatory pain. The aim of the study was to investigate and compare the antidepressant-like effects of a DOR agonist, SNC80, and a tricyclic antidepressant, amitriptyline, following intracerebroventricular (i.c.v.) administration in rats under different states. The forced swim test was used to determine the antidepressant-like effects of test compounds. Complete Freund’s adjuvant was injected subcutaneously into the right hind paw of rats to elicit inflammatory pain. Corticosterone was injected subcutaneously once per day for 21 days to induce chronic stress. The western blot was used to quantify the levels of DOR protein on plasma membrane in the hippocampus of rats under inflammatory pain or chronic stress. In addition, antagonist experiment was conducted to verify the receptor mechanism underlying the antidepressant-like effects of DOR agonist. Results indicated that i.c.v. SNC80 and amitriptyline dose-dependently produced antidepressant-like effects in rats under normal state. More importantly, the potency of SNC80-induced antidepressant-like effects, but not amitriptyline, was enhanced in rats under inflammatory pain. In addition, up-regulation of supraspinal DORs was time-dependently associated with enhanced antidepressant-like effects of SNC80 in rats under inflammatory pain. On the other hand, SNC80 did not produce enhanced antidepressant-like effects, and DOR density was not changed in rats under chronic stress. This study provides evidence of the DOR agonist’s state-dependent effects and suggests that DOR agonists may be more effective as potential antidepressants for patients with depression comorbid with chronic pain. en_US dc.description.tableofcontents 摘要.. IAbstract IIIndex IVFigure Index VIIntroduction 1Definition of depression 1Etiology of depression 2Medications of depression 4Introduction of delta opioid receptor 6Antidepressant-like effects of DOR agonists 8Relationship between antidepressants and BDNF 10Potential limitation of DOR agonists 11Functions of DOR agonists under inflammatory pain 13Aim.. 17Methods 18Animals 18Intracerebroventricular surgery 18Drug treatment 18Procedures 19Experimental design 26Statistical analysis 28Results 29Antidepressant-like effects of SNC80 and amitriptyline in rats under normal state 29Effects of naltrindole on the activity of SNC80 and amitriptyline in the FST under normal state 29Antidepressant-like effects of SNC80 in rats under inflammatory pain 30Dose-response curves of SNC80 in rats under inflammatory pain 31Table of ED50 values of SNC80 on antidepressant-like effects in rats under inflammatory pain 32Antidepressant-like effects of amitriptyline in rats under inflammatory pain 32Identification of DOR densities in hippocampus of rats under inflammatory pain 33Mean body weight of rats under chronic stress 34Antidepressant-like effects of SNC80 in rats under chronic stress 35Identification of DOR densities in hippocampus of rats under chronic stress 36Discussion 37References 48Figure description 67Figures 70 zh_TW dc.format.extent 963815 bytes - dc.format.mimetype application/pdf - dc.language.iso en_US - dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G0096752003 en_US dc.subject (關鍵詞) 憂鬱症 zh_TW dc.subject (關鍵詞) 發炎性疼痛 zh_TW dc.subject (關鍵詞) 長期壓力 zh_TW dc.subject (關鍵詞) 類鴉片delta受體 zh_TW dc.subject (關鍵詞) 制效劑 zh_TW dc.subject (關鍵詞) depression en_US dc.subject (關鍵詞) inflammatory pain en_US dc.subject (關鍵詞) chronic stress en_US dc.subject (關鍵詞) delta opioid receptor en_US dc.subject (關鍵詞) agonist en_US dc.title (題名) 慢性疼痛或壓力情境對於類鴉片delta受體的調節與其抗憂鬱功能的改變 zh_TW dc.title (題名) Effects of chronic pain or stress on the modulation of delta opioid receptor and its mediated antidepressant-like effect en_US dc.type (資料類型) thesis en dc.relation.reference (參考文獻) Adachi, M., Barrot, M., Autry, A. 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