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研究生:李嘉綺
研究生(外文):Chia-chi Li
論文名稱:代謝性麩胺酸第五型受體調控甲苯引起的行為及神經化學反應
論文名稱(外文):Metabotropic glutamate 5 receptors regulate the behavioral and neurochemical responses to toluene
指導教授:陳慧諴
指導教授(外文):Hwei-hishen Chen
學位類別:碩士
校院名稱:慈濟大學
系所名稱:藥理暨毒理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2006
畢業學年度:94
語文別:中文
論文頁數:58
中文關鍵詞:甲苯代謝性麩胺酸第五型受體
外文關鍵詞:Metabotropic glutamate 5 receptorstoluene
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甲苯是一種廣泛使用的有機溶劑,具有神經毒性。NMDA受體為甲苯作用標的之一,而mGluR5具有調控NMDA受體的功能。本研究之目的為探討mGluR5在甲苯所引發的行為反應及神經傳導物質的釋放中,所扮演的角色。利用側腦室注射的方式給予CHPG (mGluR5作用劑)或是MPEP (mGluR5 拮抗劑)後,再以急性腹腔注射甲苯。發現CHPG可以有效的去減弱甲苯所造成的體溫下降,運動協調能力下降及學習和記憶的損傷;MPEP則會增加甲苯所造成的體溫下降,延後運動協調能力的恢復時間,增加運動活性及加重學習和記憶的損傷。此外,Chelerythrine chloride (1 nmol, PKC 的拮抗劑),則可回復CHPG對甲苯的作用。微透析實驗結果發現甲苯會造成mPFC (medial prefrontal cortex) 中麩胺酸的釋放下降;而CHPG也會去減弱甲苯所造成的麩胺酸釋放下降。以上結果顯示,mGluR5經由活化PKC這個路徑,可以有效的去調節甲苯所引起的行為及神經化學物質釋放反應。
Toluene is a widely used neurotoxic organic solvent. NMDA receptor is one of the toluene’s action sites. The mGluR5 has been reported to regulate NMDA receptor function. The role of mGluR5 in toluene-induced behavioral and neurochemical responses was examined. Sprague-Dawley rats were pretreated with mGluR5 agonist (RS)-2-chloro-5-hydroxyl penyl-glycine (CHPG) and antagonist 2-methyl-6-(phenylethynyl)-pyridine(MPEP) followed by administration of toluene to induce hypothermia, motor incoordination and learning impairment. Toluene-induced hypothermia, motor incoordination and learning impairment were attenuated and enhanced by CHPG (50 nmol), and MPEP (50 nmol), respectively. Moreover, chelerythrine chloride (1 nmol), a protein kinase C inhibitor, reversed the attenuating effects of CHPG on toluene-induced behavioral responses. Microdialysis showed that toluene caused a reduction of the levels of extracellular glutamate in medial prefrontal cortex (mPFC), which was reversed by CHPG. These results suggest that mGluR5 modulate toluene-induced behavioral and neurochemical responses which were associated with activation of protein kinase C pathway.
目錄表------------------------------------------------------------------------- 1
縮寫 --------------------------------------------------------------------------- 2
英文摘要----------------------------------------------------- ----------------- 3
中文摘要----------------------------------------------------------------------- 4
壹、背景介紹----------------------------------------------------------------- 5
貳、實驗目的----------------------------------------------------------------- 13
叁、實驗材料與方法-------------------------------------------------------- 13
肆、統計分析----------------------------------------------------------------- 24
伍、實驗結果----------------------------------------------------------------- 25
陸、討論----------------------------------------------------------------------- 30
柒、結論----------------------------------------------------------------------- 36
捌、參考文獻----------------------------------------------------------------- 37
附圖---------------------------------------------------------------------------- 44
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