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研究生:陳志豪
研究生(外文):Chen, Chih-Hao
論文名稱:母鼠長期給予嗎啡對幼鼠腦內mu-型類鴉片受體及NMDA受體的影響
論文名稱(外文):The effect of chronic morphine treatment in dam rats on the brain mu-opioid receptor and NMDA receptor of the offsprings
指導教授:陶寶綠
指導教授(外文):Tao, Pao-Luh
學位類別:碩士
校院名稱:國防醫學院
系所名稱:藥理學研究所
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:1995
畢業學年度:83
語文別:中文
論文頁數:87
中文關鍵詞:嗎啡受體結合實驗自體放影射顯影mu-型類鴉片受體NMDA-受體3H-
外文關鍵詞:morphinereceptor bindingautoradiographyMu-receptorNMDA-
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目前已知具有使用嗎啡習慣的婦女易產下學習記憶方面不正常的嬰兒,其
病理機轉並不清楚。本實驗目的係探討母鼠長期給予嗎啡後,對所生幼鼠
在不同時期腦內mu-型類鴉片受體和NMDA受體是否受到影響。實驗動物為
週齡12週S.D.(Sprague-Dawley) 雌鼠,分為實驗組和控制組。實驗組以
AD50(2 mg/kg) 為初始劑量,皮下注射,早晚各 給一次藥,每隔七天劑
量增加 1 mg/kg ,給藥一週後開始進行交配繁殖,各胎幼鼠出生第 0天(
P0),第5天(P5),第14天(P14),第30天(P30) 取腦組織備用,再以試管
內受體結 合實驗和自體放射顯影(autoradiography)的方法來觀察受體變
化。試管內受體結合實驗 中以0.05 -5 nM之3H-DAMGO作mu-受體總量結合
,以 5 μM DAMGO作非特異性結合; 而NMDA受體在試管內結合實驗是
以3-60nM 3H-TCP(Tenocyclidine Hydrochloride)作總量結合,TCP 作非
特異性結合 3H-DAMGO作mu-型類鴉片受體或NMDA受體之總量結合,以300
nMDAMGO或100μM。而在自體放射顯影則以40nM3H-glutamate或0.6nM之
NMDA作非特異性結合,由自體放射顯影則可進一步觀察腦組織中不同區域
的受體變化。實驗結果發現 1.幼鼠全腦之 mu-型類鴉片受體密度在第5天
後逐漸增加,其對 3H-DAMGO 親和力不變。嗎啡長期給予母鼠所生幼鼠與
對照組在全腦 mu-類鴉片幼鼠受體密 度方面並無差異。2.正常幼鼠發育
時在第14天NMDA受體密度達到最高,長期給予母鼠嗎啡所生之幼鼠在第14
天時並無此增加的趨勢。3.mu-型類鴉片受體自體放射顯 影實驗中長期給
予母鼠嗎啡所生之幼鼠在第5天時,在striatum以及amygdala明顯 比正常
幼鼠減少;在第 14天時在 striatum, amygdala 以及 thalamus 明顯比
正常幼鼠 減少。 4.NMDA受體自體放射顯影實驗中,對照組NMDA受體在
第14天時密度增加到最多,而長期給予嗎啡之幼鼠在第14天時,受體則無
正常幼鼠增加的現象。綜合以上實驗結果證實,長期給予母鼠嗎啡會影響
到子代發育過程某些時期,腦內 mu- 型類鴉片受體和NMDA受體的發育。
因此而造成子代何種缺陷,則有待進一步的探討。

Early exposure of pregnant animals to morphine is known to
cause retardation in neurobiological development resulting in
learning and memory disabilities of offsprings.The present
study examined the density of brain mu-opioid and NMDA receptor
of offsprings during differential development both in untreated
and chronic morphine treated group.Female Sprague-Dawley rats
(12 weeks old) were given morphine via subcutaneous twice daily.
Dam rats initial administered morphine(2 mg/kg)twice a day for
7 days ,then began to mate.The dosage of morphine increased 1
mg/kg each week until parturition.After the newborns were born,
dam rats were treated with morphine by increasing dosage of 1mg/
kg every two weeks until 30th day.The rat pups of each litter
were sacrificed by decapitation on day of parturition(p0),5(
p5),14(p14),or30(p30) days postnatal.Mu-opioid receptor binding
assays were carried out in triplicate with [3H]-DAMGO,using an
excess of unlabelled DAMGO to determine the nonspecific binding.
NMDA receptor binding assays were carried out with [3H]-TCP in
the presence of glycine,NMDA ; and using excess of unlabelled
TCP to determine the nonspecific binding.Measures of affinity
and number of binding sites were obtained by using the curve-
fitting program "Ligand".In autoradiography study,[3H]-DAMGO or
[3H]-Glutamate were used to determine mu-opioid or NMDA
receptor total binding. Nonspecifiwas defined by the addition
of unlabelled DAMGO or Receptor binding Results were quantified.
These data demonstrate that mu-opioid receptors and NMDA
receptors in the brain of offsprings during develpment are
affected by chronic treatment of morphine in dam.

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