探討阿糖胞苷在條件化恐懼中扮演的急性影響

To study the acute effect of cytosine arabinoside on the conditioned fear

楊士德(Yang Sh-Te)

指導教授 ： 呂國棟

國立臺灣師範大學/理學院/生命科學系/碩士(2009年)

摘要

阿醣胞苷是胞嘧啶的異構物長期用於急性白血病的治療，但是阿醣胞苷同時也是實驗上常用於抑制神經新生方面的研究藥物。在前人研究中指出當條件化恐懼訓練之後投予阿醣胞苷於大白鼠 (1000 mg/kg body weight, i.p) 具有抑制條件化學習，這項研究支持了 DNA 重組參予條件化恐懼學習的過程，但是阿醣胞苷是否還有除了影響 DNA 重組以外的功能參予其中呢？本實驗利用大白鼠的離體胞外電生理記錄法 (in vitro extracellular electrophysiological recording)、恐懼所促進的驚跳反應 (fear-potentiated startle)、TdT-mediated dUTP end labeling (TUNEL) 染色來進行討論。
從實驗結果顯示經由阿醣胞苷處理的大白鼠腦片具有抑制杏仁核興奮性突觸後電位 (EPSP) 的能力，並且在大白鼠行為訓練後二十四小時中樞投予阿醣胞苷可以影響投予藥物後三小時的恐懼記憶，但是不影響投予藥物後六小時的恐懼記憶，證實阿醣胞苷對恐懼記憶的影響隨時間遞減。由於在先前的研究中指出高劑量的阿醣胞苷具有神經毒殺的效果，因此實驗利用 TUNEL 染色來作為判斷投予此實驗劑量的阿醣胞苷對神經是否有毒殺效果。實驗結果顯示於三小時以及六小時的老鼠腦片中並沒有發現有細胞凋亡的現象。
最後，實驗結果支持了阿醣胞苷在短時間內可能會影響神經突觸功能。期盼未來可以對阿醣胞苷影響神經傳導上有更明確的機制，並且可以更深入的了解阿醣胞苷對於人類行為可能產生的影響。

關鍵字

阿醣胞苷 ； 恐懼所促進的驚跳反應

並列摘要

Cytosine arabinoside (Ara-C) is a cytidine analogue which is routinely used in chemical therapy of acute myeloid leukemia. It has been also used as an anti-neurogenesis agent. Recent study showed injection of ara-C in rats (1000 mg/kg body weight, i.p) after fear condition learning can affect consolidation. They concluded that DNA recombination is an essential process for the consolidation of conditioned fear. We concerned that ara-C treatment may have other effects on the fear conditioning instead of inhibition DNA recombination. We used in vitro electrophysiological recording, fear-potentiated startle paradigm and TUNEL assay to test this amygdala.
Our results showed superficial infusion of ara-C inhibited EPSP level in the amygdala region. Additional groups of animal were subjected for fear-potentiated startle test. Ara-C was administrated into the bilateral ventricle 24 hrs after fear conditioning. Results showed that acute ICV infusion of ara-C blocked expression of learned fear in a temporal pattern. It had significantly blockage effect of conditioned fear within a 3 hrs interval but did not show any inhibitory effect in the 6 hrs interval. Previous studies suggested higher doses of ara-C have neurotoxic effect. We used TUNEL assay to test the possible toxic effect of the ara-C dose we used in this experiment. Parallel groups of animals were scarified exactly the same time point according to the behavioral test results. No significant positive signal of TUNEL assay had been found in the ara-C treated animals.
In conclusion, results obtained from this study suggest ara-C may have acute effects on the synaptic transmission. Further experiments are required to elucidate the detail mechanism of ara-C acute effects on the synaptic transmission and to obtain a clear picture regard to the possible behavioral toxic effect of ara-C in human.

並列關鍵字

Cytosine arabinoside ； Fear-potentiated startle

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