強迫症患者中常發現眼眶額葉皮質過度活化，以及對恐懼消除學習的缺陷。眼窩額葉皮質可再分為外側、內側眼窩額葉皮質。過去的研究指出，外側及內側眼窩額葉皮質均有神經投射到恐懼相關迴路的腦區。其中包含杏仁核、海馬迴、以及內側前額葉，上述腦區在恐懼制約及消除行為中都佔有相當重要的角色。在我們實驗室先前的研究中，我們發現活化外側、內側眼窩額葉皮質均會干擾恐懼消除的學習，在這個實驗中，我們則要研究活化或抑制眼窩額葉皮質對於帕夫洛夫恐懼制約學習的影響。
我們的行為程序是三天的帕夫洛夫恐懼制約及測驗，以大鼠不動的程度作為恐懼反應的指標。在第一天恐懼制約前，會依照活化、抑制或控制組分別打入對應藥物，隨後制約組的大鼠會接受聲音與電擊的配對；不制約組的大鼠則只接受聲音。在第二天，所有動物進入前一天制約的情境以測試對制約情境的恐懼。在第三天，所有的動物會進入新情境，並接受聲音刺激以測試其對制約刺激的恐懼反應。
我們的實驗結果顯示，在執行恐懼制約之前活化外側眼窩額葉皮質，動物會表現對制約刺激恐懼的學習降低的趨勢，活化內側眼窩額葉皮質則會同時干擾情境及制約刺激恐懼的學習，但在執行恐懼制約之前抑制外側或內側眼窩額葉皮質，均不會影響情境或制約刺激恐懼的學習。綜合上述實驗結果，我們結論活化眼窩額葉皮質會干擾動物恐懼制約記憶習得，並且因為抑制眼窩額葉皮質不影響動物恐懼制約記憶習得，故推測眼窩額葉皮質不會主動參與在動物恐懼制約的學習行為。

Obsessive-compulsive disorder (OCD) patients were usually found with the hyperactivation of the orbitofrontal cortex (OFC) and a deficit in fear extinction learning. The OFC can be subdivided into the lateral OFC (lOFC) and the medial OFC (mOFC). Previous studies have suggested that both subregions are involved in the modulation of negative emotions. However, how aberrant activation of the OFC interacts with the encoding of Pavlovian fear remains unknown. In this study, the lOFC or the mOFC was pharmacologically activated or inactivated before the fear conditioning on Day 1, followed by a context test on Day 2 and a tone test on Day 3 in male Long-Evans rats. We found that for the animals that underwent fear conditioning under aberrant activation of either the lOFC or the mOFC, they showed normal within-session fear expression. However, the acquisition/consolidation of contextual fear was impaired under mOFC activation, while the acquisition/consolidation of cued fear was impaired under either the lOFC or the mOFC activation, in that these animals showed lower freezing compared to controls during the retrieval test. On the other hand, for the animals that underwent fear conditioning under inactivation of either the lOFC or the mOFC, they showed normal within-session fear expression, as well as intact encoding of both the contextual and cued fear. Together, our results suggested that the OFC was not actively engaged in the acquisition of Pavlovian fear conditioning, but aberrant activation of the OFC impaired fear learning.

中文摘要...............................................i
Abstract..............................................ii
致謝..................................................iii
Disclosure.............................................iv
Table of content........................................v
Introduction............................................1
Materials and Methods...................................3
Subjects................................................3
Surgery.................................................3
Behavioral apparatus....................................3
Behavioral procedures...................................4
Drug infusion...........................................4
Histology...............................................5
Behavioral analysis.....................................5
Results.................................................6
Experiment 1: Fear encoding under lOFC activation.......6
Experiment 2: Fear encoding under lOFC inactivation.....7
Experiment 3: Fear encoding under mOFC activation.......8
Experiment 4: Fear encoding under mOFC inactivation....10
Discussion.............................................12
Figures................................................15
Reference..............................................21

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