Epinephrine Modulation of Fear Conditioning under Awake and Anesthetic States

時間接近性向來被視為造成連結學習的重要因素，但是刺激重要性所引發的興奮狀態也可以左右學習的強弱。人類的研究中發現，在學習時呈現嫌惡性刺激可以使得學習在麻醉狀態下發生。嫌惡刺激會引發身體釋放壓力激素，其中腎上腺素已被證明是調節記憶的內在因子。因此，嫌惡刺激所引發腎上腺素釋放的機制，可能足以獨立於主觀意識之外，傳達一般性的興奮訊息，影響中樞神經系統的學習記憶機制，使學習得以在麻醉狀態下發生。本研究企圖利用條件化僵直行為以及恐懼增益驚跳反應作為恐懼學習典範，驗證此一假說。研究的策略是先建立腎上腺素可以增強清醒狀態下的恐懼條件學習，建立此現象之後，再讓此恐懼條件學習在麻醉的狀態下進行，進行探討麻醉狀態下之恐懼條件學習是否受到周邊腎上腺素調節而增強。本研究發現在清醒狀態下進行刺激配對訓練，訓練後周邊注射腎上腺素，之後測試對特定條件刺激、訓練情境以及兩者共同呈現所分別表現的僵直反應。研究結果發現，無論利用視覺或是聽覺刺激作為條件刺激，腎上腺素均不影響條件化僵直反應的學習。相對的，訓練前周邊注射每公斤體重0.01毫克或是0.1毫克腎上腺素，有效增進清醒狀態下一次刺激配對的恐懼增益驚跳反應學習。訓練前周邊注射每公斤體重0.1毫克以及1.0毫克腎上腺素，有效增進麻醉狀態下五次刺激配對的恐懼增益驚跳反應學習。本研究顯示，在學習歷程中，除了主動注意可以反映刺激訊息的重要性外，腎上腺素可以在麻醉的無意識狀態下，表徵刺激以及經驗的重要性，傳達一般性的興奮訊息進入中樞神經系統，影響學習的發生。Temporal contiguity has been proved to be one of the most influential factors in associative learning. Stimulus saliency may also contribute significantly to learning. However, learning nonetheless happens without intention or even awareness. Thus, there should be mechanisms subserving the saliency function other than subjective awareness. Evidence indicated that learning under anesthesia occurs more during presentation of noxious stimuli that may release epinephrine. This study aimed to test whether epinephrine also modulates learning and memory processes under an anesthetic state. Conditioned freezing and conditioned potentiation of startle were chosen to assess memory of fear conditioned to a specific stimulus, the training environment or both using shock as unconditioned stimulus. The result showed that post-training epinephrine injections under an awake state did not modulate subsequent freezing behavior induced by the specific conditioned stimulus, the training environment or both of them. In contrast, pre-training epinephrine subcutaneous injection enhanced memory of fear-potentiated startle formed under awake and anesthetic states. In conclusion, epinephrine may be one of the mechanisms representing the stimulus saliency under awake and even anesthetic states.第一章緒論……………………………………………………………1 第二章實驗材料與方法………………………………………………14 第三章實驗結果………………………………………………………20 第四章綜合討論………………………………………………………36 參考文獻………………………………………………………………48 附圖說明………………………………………………………………59 附圖……………………………………………………………………6