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研究生: 李曉薇
Lee, Hsiao-Wei
論文名稱: 探討在自發性失神癲癇大鼠長期給予lamotrigine對癲癇與似焦慮/憂鬱行為之影響
Chronic lamotrigine treatment in seizure and anxiety-/depression-like behaviors of the rat with spontaneous absence epilepsy
指導教授: 蕭富仁
Shaw, Fu-Zen
學位類別: 碩士
Master
系所名稱: 社會科學院 - 認知科學研究所
Institute of Cognitive Science
論文出版年: 2010
畢業學年度: 98
語文別: 英文
論文頁數: 40
中文關鍵詞: LamotrigineLong-Evans大鼠棘徐波焦慮行為憂鬱行為開放空間架高十字迷宮糖水測試強迫游泳測試
外文關鍵詞: Lamotrigine, Long-Evans rats, spontaneous spike-wave discharges, anxiety, depression, open field, elevated plus maze, sucrose consumption, forced swimming
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  • Lamotrigine (LTG)是一種新型的抗癲癇藥物,在臨床上常用來治療失神性癲癇。然而,目前LTG在癲癇動物實驗結果卻出現與臨床失神癲癇病患不一致的現象,結果的主要差異可能是給LTG的方式不同(單次[動物實驗]vs長期[臨床使用])所造成。為了進一步釐清LTG在失神癲癇動物實驗的效果以及了解LTG對於癲癇併發產生焦慮與憂鬱的影響,本論文比較會自發性產生棘徐波(spike-wave discharge, SWD)的Long-Evans大鼠在長期給予LTG或飲用水之後發現:(1)、單次給予LTG治療無法抑制SWD;(2)、經過35天的LTG治療,能夠有效抑制SWD發作的總時間、SWD次數、以及SWD平均時間,而控制組大鼠則沒有統計上的差異;長期給予LTG大鼠會比控制組大鼠出現較長時間穿越開放空間(open field test)的中央區域以及較長時間探索架高型十字迷宮(elevated plus maze test)的開放支架等現象,其結果都達到統計上顯著的差異;(4)、在強迫游泳測試(forced swimming test)中,長期給予LTG大鼠的不動時間顯著短於控制組大鼠的不動時間。本論文證實LTG在以臨床類似狀況下長期給予之後可以顯著地抑制失神癲癇,並且同時改善失神癲癇引發之似焦慮與似憂鬱行為。

    Lamotrigine (LTG), an antiepileptic drug, is a prescription for both convulsive and absence seizures in clinic. However, LTG effects are quite controversial between epileptic animal experiments and patients. Different administering route and duration may be reasons to produce the discrepancy. To understand LTG effect on absence seizures and on its comorbidity of anxiety and depression, LTG (10 mg/kg) or water was chronically peroral administered twice daily on Long-Evans rats with spontaneous spike-wave discharges (SWDs) for 35 days. Our results showed that acute administration of LTG had no benefit in suppression of absence seizures. Total SWD duration, SWD number, and mean SWD duration were significantly decreased in rats received 35-day LTG compared to those of rats with vehicle. Moreover, rats having LTG treatment displayed significantly longer duration entering the central zone of an open field and longer duration exploring open arm of an elevated plus maze compared to those of the control group. Immobile duration during a forced swimming test was significantly shorter in rats with LTG than those of rats with vehicle. Our results suggest that chronic LTG treatment has a great benefit on suppression of absence seizures and also ameliorates anxiety and depression.

    中文摘要 I Abstract II Acknowledgment IV Content VI List of Figures VIII Abbreviation IX Introduction 1 Absence epilepsy 1 Depression/anxiety 2 Long-Evans rats with spontaneous spike wave discharges 3 Lamotrigine 4 Methods 6 Animal preparations and recordings 6 Drug Preparation 7 Behavioral tests 8 Procedural of experiment 11 Statistical analysis 12 Results 13 Electroencephalogram recordings 13 Open field test 15 Elevated plus maze test 15 Sucrose consumption test 16 Forced swimming test 16 Discussion 18 Major findings 18 Lamotrigine treatment 18 Anxiety-like behaviors under chronic lamotrigine 19 Depression-like behaviors under chronic lamotrigine 20 Conclusion 23 Future work 24 References 25 Figures 33

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