各式各樣的外在環境刺激進入了人類大腦的杏仁核，經由與睡眠相關的恐懼記憶形成的機轉而形成相關的精神症狀。在以前的醫學文獻裡，雖然潛在的機轉尚未被釐清，但已經陸續有許多研究提出剝奪睡眠 (特別是剝奪動眼期睡眠) 可能影響學習與記憶。在這篇研究裡，我們發現剛獲得的情緒性記憶會受到某一段特定時期的動眼期睡眠剝奪之影響而減弱，這個動眼期睡眠窗(paradoxical sleep window)坐落在訓練後的第十三小時至第二十四小時之間。「記憶再現」(memory retrieval)所導致老鼠杏仁核內之Akt及MAPK等蛋白磷酸酶被磷酸化的情形也可以經由動眼期睡眠剝奪之影響而消弱。在訓練過程之前進行動眼期睡眠之剝奪並不會影響學習記憶的結果，這個部分顯示：動眼期睡眠剝奪不會對於「記憶獲得」（memory acquisition）產生作用。更進一步，動眼期睡眠剝奪又與一種同時具有蛋白去磷酸酶與脂質去磷酸酶雙重作用的蛋白質—PTEN的表現增加有關聯性。與對照組實驗結果明顯不同，訓練後第十三小時至第二十四小時之間的動眼期睡眠之剝奪會引起PTEN表現量的上升。而且，在杏仁核內注射PTEN的antisense型之寡核甘酸會防止動眼期睡眠剝奪所導致的蛋白質磷酸化之減少以及恐懼記憶之減弱情形，相反地，如果把PTEN的antisense型寡核甘酸置換成sense型或scrambled型之寡核甘酸，也就沒有上述結果。綜合這些研究發現，我們得到一個明確的結論：動眼期睡眠之剝奪會經由活化PTEN而干擾了「記憶保留」(memory retention)的過程。
　　另一方面，我們希望找出合適的臨床藥物以阻斷恐懼記憶的形成過程，以期望有效地預防焦慮症形成，降低焦慮症發生率，減少醫療資源之耗費。研究結果顯示：在恐懼記憶訓練後之十二小時內使用特定藥物（特別是lorazepam與midazolam）可以有效減少恐懼記憶的產生，如果能立即使用藥物，則不僅只能選用lorazepam與midazolam，使用情緒穩定劑（carbamazepine、valproate）或乙型交感神經抑制劑也有不錯的效果。如果使用上述有效的藥物，則越早使用藥物，預防效果越好。另外，使用lorazepam與midazolam阻礙恐懼記憶形成的效果與使用劑量之間有正向相關性。但是使用抗憂鬱劑，例如：三環抗憂鬱劑與選擇性5-羥色胺再吸收抑制劑，都沒有明顯效果。綜合上述結果，我們提出一個研究與治療焦慮症的新方向。

　　Several kinds of environmental stimuli enter the amygdala and result in related mental symptoms by the sleep-dependent mechanism responsible for fear memory formation. Although the underlying mechanism is not elucidated, it has been repeatedly postulated that deprivation of sleep, rapid eye movement (REM) sleep in particular, affects learning. Here we report that memory for newly acquired information is impaired following a specific period of REM sleep deprivation (REMD). The paradoxical sleep window (PS window) is ranged from the 13th to the 24th hours after training. REMD given before training is without effect suggesting the lack of effect on the acquisition of memory. Memory retrieval-induced phosphorylation of protein kinases in the rat amygdala is abrogated by REMD that is associated with an increase in the expression of a dual protein/lipid phosphatase PTEN. REMD during the PS window induced a significant increase in the expression of PTEN as compared with the control experiments. Intra-amygdala administration of antisense but not sense or scrambled oligonucleotides for PTEN prevents REMD-induced decrease in protein phosphorylation and impairment of fear memory. Thus, REMD interferes with the process of memory retention via activation of PTEN.
　　In addition, we aim to identify the optimum clinical drugs for preventing the formation of fear memory, therefore decreasing the incidence of anxiety disorders and the economical burden of healthcare system. Our results reveal that when drugs are administered immediately after fear training, lorazepam, midazolam, propranolol, carbamazepine and valproate are effective in disrupting the fear memory formation. However, when drugs are administered 6 hours after fear training, only lorazepam, midazolam, carbamazepine and valproate are effective. Furthermore, when drugs are administered 12 hours after fear training, only lorazepam and midazolam are effective. If we use theses drugs sooner, the effect will be better. However, antidepressants including tricyclics and SSRIs are ineffective at all the three time points. The further results show that there is a positive dose-effect relationship of lorazepam and midazolam on the prevention for fear memory formation. Consequently, we recommend such a new approach to anxiety disorders.

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