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研究生:鄭淑云
研究生(外文):Shu-Yun Cheng
論文名稱:間歇性低氧對安非他命處理的大白鼠腦中多巴胺變化之效應
論文名稱(外文):Effects of Intermittent Hypoxia on Brain Dopamine Levels in Rats Treated with Amphetamine
指導教授:王錫崗王錫崗引用關係
指導教授(外文):Paulus S. Wang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:67
中文關鍵詞:間歇性低氧安非他命多巴胺多巴胺傳輸蛋白囊泡單胺傳輸蛋白
外文關鍵詞:Intermittent hypoxiaAmphetamineDopamineDopamine transportervesicular monoamine transporter
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 安非他命具有神經毒性且因藥物濫用以致成癮;同時尚易影響腦部調控蛋白,例如多巴胺傳輸蛋白(DAT)以及囊泡單胺傳輸蛋白(vesicular monoamine transporte),表現異常進而改變行為。目前對於安非他命濫用導致之副作用尚未找到有效的解決方法,仍有待研究。我們過去的研究發現,間歇性低氧造成間腦細胞外液多巴胺濃度降低,並使血漿泌乳素濃度上升。本實驗中,我們將針對間歇性低氧對安非他命處理之大鼠腦中多巴胺變化之效應進行研究。大鼠隨機分為四組,依序為常氧對照組,間歇性低氧組,安非他命組,安非他命後給予間歇性低氧組。常氧對照組及間歇性低氧組均腹腔注射生理食鹽水以作為對照﹔間歇性低氧組係置於12% O2 及 88% N2之低氧箱每天八小時,連續七天,安非他命組則是每公斤腹腔注射五毫克,連續七天﹔第四組則是連續七天注射安非他命後再置入12% O2 及 88% N2之低氧箱每天八小時,連續七天。各組前處理後,利用微透析方式每二十分鐘收集腦脊髓液並利用高效液相層析儀/電化學檢測系統分析多巴胺濃度變化﹔血漿泌乳素濃度則利用頸靜脈採血,再以放射免疫法分析。結果顯示,間歇性低氧對於腦中不同核區位置有不同影響:間歇性低氧能降低前額葉皮質區多巴胺釋放,增加紋狀體區多巴胺釋放﹔然在安非他命刺激後再給予間歇性低氧組中,無論是前額葉皮質區或紋狀體區多巴胺釋放均會增加。同時,若於核區給予血管張力素II,無論在前額葉皮質區或紋狀體區均可增強多巴胺釋放之效應,且在安非他命後再給予間歇性低氧的大鼠腦中效果更為顯著。除此之外,血漿泌乳素濃度在低氧組會增高。另外,間歇性低氧後給予安非他命會造成前額葉皮質區與中底下視丘之tyrosin hudroxylase表現增加,且不論是間歇性低氧、安非他命單獨或合併處理,VMAT-2在前額葉皮質區、紋狀體、中底下視丘以及小腦內的含量均會下降,而DAT無論是在紋狀體,前額葉皮質區,中底下視丘或小腦,其蛋白表現並不因間歇性低氧或安非他命處理而改變。由此研究我們推測,間歇性低氧會造成腦部多巴胺釋放有所改變,且對於不同核區,其影響之機轉亦不同,在調控腦中分子代謝上其扮演一重要角色。
 Amphetamine is a highly addictive drug of abuse that is neurotoxic to dopamine terminals. Amphetamine changes the expression of the dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT 2) in rat brain and then causes the unusual behavior. However, the effective ways to cure problems of drug abuse are still open to study. We have previously found that intermittent hypoxia reduces the basal level of dopamine in the diencephalon and increases plasma prolactin concentration. In the present study, the effect of intermittent hypoxia on the dopamine release in rats treated with or without amphetamine was investigated. Rats were divided into four groups including normoxia, hypoxia, amphetamine treatment, and amphetamine plus hypoxia groups. The normoxia and hypoxia groups were injected with normal saline as vehicle control. The rats in hypoxia group were housed in a box of 12% O2 plus 88% N2, 8 h per day for 7 days. These rats were injected with or without amphetamine daily (5 mg/kg) for 7 days. The rats treated with amphetamine plus hypoxia were injected with amphetamine daily for 7 days and then housed in a hypoxic box for 8 h daily for 7 days. After pretreatment, the cerebrospinal fluid was collected by microdialysis every 20 min and the dopamine levels in the dialysates were detected by HPLC. Rat plasma was collected every 40 min and the prolactin concentration was measured by radioimmunoassay. We found that intermittent hypoxia reduced the concentration of dopamine in the media prefrontal cortex and increased that in the striatum. Dopamine levels were increased despite rats treated with intermittent hypoxia or with amphetamine plus intermittent hypoxia. Furthermore, intermittent hypoxia failed to lower the responses to Ang II in the media prefrontal cortex and striatum but enhanced the responses. The plasma prolactin concentration increased in the hypoxic groups. Otherwise, amphetamine plus intermittent hypoxia would increase tyrosine hydroxylase expression in the prefrontal cortex. At the same time, intermittent hypoxia or amphetamine treatment would decrease the expression of VMAT-2 in the rat brain. However, whether rats treated with amphetamine or intermittent hypoxia, the expression of dopamine transporter did not changed. These data suggest that intermittent hypoxia would alter the dopamine release and change the protein expression in different nucleus in the brain. Intermittent hypoxia did play an important role in regulating dopamine metabolism in rat brain.
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