在Long Evans (LE)大鼠長時間腦電波記錄中常觀察到一種自發性7-12 Hz棘徐波放電(spike-wave discharge, SWD)，經由電生理及藥理測試後已證實此棘徐波放電與人類失神性癲癇類似。目前用來作為失神性癲癇動物模式多為近親交配(WAG/Rij)或是經由篩選(GAERS)而培育出的癲癇大鼠，不同於LE品系為自然非近親交配鼠種。爲建立LE大鼠完整的基礎資料，本實驗在3, 6, 12月大的公母鼠進行額葉腦電波記錄，並計算出在兩小時記錄中SWD產生次數，發現在三個月大LE大鼠已出現SWD，且次數會隨著年紀增長而增加，到六個月大時達到最高峰，但這個趨勢無性別差異。利用陰道抹片判斷三個月大大鼠的時動情週期，也發現在動情前期SWD次數與時間相較其於動情周期其他期間較高，而且在連續記錄腦電波48小時發現SWD具有日變節律。利用焦慮行為評估工具〈架高型十字迷宮、開放空間、亮暗箱〉以及憂慮行為評估工具〈強迫游泳測試〉來比較Wistar與LE大鼠行為參數，另外在LE大鼠給予Ethosuximide (ETX, 100 mg/kg, i.p.)以完全抑制SWD，以便探討SWD對於LE大鼠的行為試驗的影響。從架高型十字迷宮與開放空間可發現大鼠移動距離隨著SWD次數的增加而減弱，這樣的運動功能抑制情況在給予ETX後則恢復正常。相對於Wistar大鼠而言LE大鼠的似焦慮程度較低且似憂鬱程度較高。而且SWD次數與似焦慮程度呈現正相關，在LE大鼠給予ETX後這種相關顯著性則幾乎完全消失，但是在似憂鬱實驗沒有發現此特徵。基於以上結果，本研究了解LE大鼠的SWD產生與年齡有關而且到六個月後達到最大值，且SWD可能會對憂鬱及焦慮有關神經網絡有不同的影響。

Spontaneous paroxysmal 7-12 Hz spike-wave discharges (SWDs), which may be associated with absence seizures based on several lines of electrophysiological and pharmacological evidences, are often observed in Long Evans rats. Compared to well-developed absence epileptic rat models, i.e., WAG/Rij and GAERS strains, the development and gender sensitivity of SWDs in Long Evans rats remains largely unknown. Moreover, the correlate of SWDs and psychological performance also remains poorly understood. To investigate these issues, skull electrodes were implanted in six groups of Long Evans rats classified by gender and age (3, 6, 12 months). The number and durations of SWDs, which were identified from 2-h recording sessions, increased as age increased and reached the maximum at 6 months old. These SWD indexes revealed no difference in gender. Moreover, the occurrence of SWDs displayed a circadian rhythm from a continuous 48-h recording. The number and duration of SWDs were slightly higher at the proestreus stage of estrus cycle. Moreover, four behavioral paradigms, including anxiety-like behavioral test (elevated plus-maze, open field and light-dark box choice) and depression-like behavioral test (forced swimming) were used to evaluate the anxiety and depression levels in both Long Evans and Wistar rats. Changes of 4 behavioral tests by the administration of ethosuximide (ETX, 100 mg/kg i.p.) were also compared in Long Evans rats. Movement in the elevated plus maze and open field tests decreased as SWD number increased, and ETX restored the motor ability. Compared to Wistar rats, Long Evans rats were the propensity of low anxiety and high depression. In addition, increase of SWD numbers was prone to increase of anxiety-like behavior, and the trend was abolished by ETX. However, no obvious trend was found between depressive-like behaviors and SWD numbers before and after ETX injection. Based on these results, we conclude that the development of SWDs in Long Evans rats is age-dependent, and SWDs may affect both anxiety- and depression-associated neural circuits differentially.

中文摘要 1
英文摘要 3
前言 4
材料與方法 11
結果 16
討論 21
結論 29
參考文獻 30
附圖 34

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