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題名 苯甲酸鈉改善K他命誘發之行為異常
Sodium benzoate ameliorates ketamine-induced behavioral disturbances作者 劉奕賢 貢獻者 陳慧諴、詹銘煥
劉奕賢關鍵詞 K他命
苯甲酸鈉
抗憂鬱效果
擬精神病行為
麻醉反應
Ketamine
Sodium benzoate
Antidepressant-like responses
Psychotomimetic behaviors
Anesthetic responses日期 2018 上傳時間 3-Sep-2018 15:52:33 (UTC+8) 摘要 K他命 (Ketamine)是一種合成的解離型麻醉劑，具有快速啟動抗憂鬱效果的作用。近年來，它成為了一種常見的濫用藥物。長期使用K他命會造成突觸功能損傷與行為異常，如 : 社交互動缺陷、認知功能障礙以及憂鬱症傾向的情形發生，亦會降低突觸相關蛋白的表現量。越來越多的研究發現，藉由增強NMDA受體的功能可以改善K他命誘導的行為異常與神經化學變化。苯甲酸鈉 (sodium benzoate)是一種右旋胺基酸氧化酵素酶抑制劑，透過增加D-serine間接增強NMDA受體功能，臨床研究顯示對思覺失調症或憂鬱症患者皆有良好的治療效果。本研究的目標在於檢測sodium benzoate是否可以保護或改善小鼠急性或重複暴露K他命情況下所導致的行為與突觸蛋白異常。結果發現，sodium benzoate在強迫游泳試驗中具有抗憂鬱效果，然而與K他命並不會產生加成的作用。Sodium benzoate增強了K他命在失去翻正反射試驗中的麻醉反應，但減弱了K他命誘導在社交互動行為與新物體辨識能力測試中的擬精神病行為。同時重複給予sodium benzoate與K他命14天顯著地減弱K他命誘導的持續性行為異常，包括社交退縮、認知障礙、類憂鬱症行為與5-HT2A受體介導頭部抽蓄反應的敏感性。此外，透過後給予sodium benzoate方式也能改善重複暴露K他命後的異常行為表現及海馬迴中突觸蛋白表現異常的影響。這些結果推測sodium benzoate可能有助於減緩使用K他命所造成的負面行為影響。
Ketamine is a synthetic dissociative anesthetic and has rapid onset antidepressant effect. It has become a common abused substance, recently. Heavy ketamine use often results in synaptic dysfunction and behavioral disturbances including depression, social deficits, cognitive impairments and decrease synapse-associated protein expression. Growing evidence shows that enhancement of NMDA receptor function can ameliorate the effects of ketamine-induced behavioral and neurochemical responses. Sodium benzoate, an inhibitor of D-amino acid oxidase, can indirectly increase the NMDA receptor function through increasing the levels of D-serine and is also beneficial to the patients with depression or schizophrenia in the clinical study. The present study examined whether sodium benzoate could protect or reverse the behavioral dysfunction and synaptic dysfunction in mice exposed to ketamine acutely or repeatedly. Our results showed that sodium benzoate has antidepressant-like responses in the forced swimming test, whereas it did not produce additive effect with ketamine. Sodium benzoate enhanced the anesthetic responses of ketamine in the loss of righting reflex test, but attenuated the ketamine-induced psychotomimetic behaviors in the social interaction test and novel object recognition test. Repeated cotreatment of sodium benzoate and ketamine for 14 days significantly attenuated ketamine-induced persistent behavioral abnormalities including social withdrawal, recognition impairment, depression-like behaviors and hypersensitiveness of 5-HT2A receptor-mediated head twitch response. Moreover, the behavioral manifestation and lower level of synaptic protein PSD-95 after repeated ketamine exposure could be ameliorated by post-treatment of sodium benzoate. 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國立政治大學
神經科學研究所
105754004資料來源 http://thesis.lib.nccu.edu.tw/record/#G0105754004 資料類型 thesis dc.contributor.advisor 陳慧諴、詹銘煥 zh_TW dc.contributor.author (Authors) 劉奕賢 zh_TW dc.creator (作者) 劉奕賢 zh_TW dc.date (日期) 2018 en_US dc.date.accessioned 3-Sep-2018 15:52:33 (UTC+8) - dc.date.available 3-Sep-2018 15:52:33 (UTC+8) - dc.date.issued (上傳時間) 3-Sep-2018 15:52:33 (UTC+8) - dc.identifier (Other Identifiers) G0105754004 en_US dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/119912 - 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) 105754004 zh_TW dc.description.abstract (摘要) K他命 (Ketamine)是一種合成的解離型麻醉劑，具有快速啟動抗憂鬱效果的作用。近年來，它成為了一種常見的濫用藥物。長期使用K他命會造成突觸功能損傷與行為異常，如 : 社交互動缺陷、認知功能障礙以及憂鬱症傾向的情形發生，亦會降低突觸相關蛋白的表現量。越來越多的研究發現，藉由增強NMDA受體的功能可以改善K他命誘導的行為異常與神經化學變化。苯甲酸鈉 (sodium benzoate)是一種右旋胺基酸氧化酵素酶抑制劑，透過增加D-serine間接增強NMDA受體功能，臨床研究顯示對思覺失調症或憂鬱症患者皆有良好的治療效果。本研究的目標在於檢測sodium benzoate是否可以保護或改善小鼠急性或重複暴露K他命情況下所導致的行為與突觸蛋白異常。結果發現，sodium benzoate在強迫游泳試驗中具有抗憂鬱效果，然而與K他命並不會產生加成的作用。Sodium benzoate增強了K他命在失去翻正反射試驗中的麻醉反應，但減弱了K他命誘導在社交互動行為與新物體辨識能力測試中的擬精神病行為。同時重複給予sodium benzoate與K他命14天顯著地減弱K他命誘導的持續性行為異常，包括社交退縮、認知障礙、類憂鬱症行為與5-HT2A受體介導頭部抽蓄反應的敏感性。此外，透過後給予sodium benzoate方式也能改善重複暴露K他命後的異常行為表現及海馬迴中突觸蛋白表現異常的影響。這些結果推測sodium benzoate可能有助於減緩使用K他命所造成的負面行為影響。 zh_TW dc.description.abstract (摘要) Ketamine is a synthetic dissociative anesthetic and has rapid onset antidepressant effect. It has become a common abused substance, recently. Heavy ketamine use often results in synaptic dysfunction and behavioral disturbances including depression, social deficits, cognitive impairments and decrease synapse-associated protein expression. Growing evidence shows that enhancement of NMDA receptor function can ameliorate the effects of ketamine-induced behavioral and neurochemical responses. Sodium benzoate, an inhibitor of D-amino acid oxidase, can indirectly increase the NMDA receptor function through increasing the levels of D-serine and is also beneficial to the patients with depression or schizophrenia in the clinical study. The present study examined whether sodium benzoate could protect or reverse the behavioral dysfunction and synaptic dysfunction in mice exposed to ketamine acutely or repeatedly. Our results showed that sodium benzoate has antidepressant-like responses in the forced swimming test, whereas it did not produce additive effect with ketamine. Sodium benzoate enhanced the anesthetic responses of ketamine in the loss of righting reflex test, but attenuated the ketamine-induced psychotomimetic behaviors in the social interaction test and novel object recognition test. Repeated cotreatment of sodium benzoate and ketamine for 14 days significantly attenuated ketamine-induced persistent behavioral abnormalities including social withdrawal, recognition impairment, depression-like behaviors and hypersensitiveness of 5-HT2A receptor-mediated head twitch response. Moreover, the behavioral manifestation and lower level of synaptic protein PSD-95 after repeated ketamine exposure could be ameliorated by post-treatment of sodium benzoate. These findings suggest that sodium benzoate might have potential to reduce negative behavioral consequences of heavy ketamine use. en_US dc.description.tableofcontents 摘要 IAbstract II目錄 IV圖表目錄 V縮寫對照表 VII壹、 背景介紹 1一、 K他命 (Ketamine) 1二、 K他命吸收與代謝 1三、 K他命作用機制 2四、 K他命的抗憂鬱效果 4五、 急性K他命造成類精神病症狀 5六、 K他命的麻醉效果 6七、 慢性K他命造成類精神病症狀 6八、 苯甲酸鈉 8貳、 研究動機與目的 10參、 實驗設計 11肆、 實驗材料與方法 12伍、 實驗數據分析 22陸、 實驗結果 23柒、 討論 33捌、 結論 40玖、 參考文獻 41壹拾、 圖表 55 zh_TW dc.format.extent 1172404 bytes - dc.format.mimetype application/pdf - dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G0105754004 en_US dc.subject (關鍵詞) K他命 zh_TW dc.subject (關鍵詞) 苯甲酸鈉 zh_TW dc.subject (關鍵詞) 抗憂鬱效果 zh_TW dc.subject (關鍵詞) 擬精神病行為 zh_TW dc.subject (關鍵詞) 麻醉反應 zh_TW dc.subject (關鍵詞) Ketamine en_US dc.subject (關鍵詞) Sodium benzoate en_US dc.subject (關鍵詞) Antidepressant-like responses en_US dc.subject (關鍵詞) Psychotomimetic behaviors en_US dc.subject (關鍵詞) Anesthetic responses en_US dc.title (題名) 苯甲酸鈉改善K他命誘發之行為異常 zh_TW dc.title (題名) Sodium benzoate ameliorates ketamine-induced behavioral disturbances en_US dc.type (資料類型) thesis en_US dc.relation.reference (參考文獻) 中文部分林仁政 (2016)。二甲基甘胺酸與三甲基甘胺酸對於K他命誘發抗憂鬱與擬精神病行為之效用 (未出版之博士論文)。國防醫學院，臺北市。英文部分Abelaira HM, Reus GZ, Neotti MV, Quevedo J (2014) The role of mTOR in depression and antidepressant responses. 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