生活上的壓力事件會增加了個體發生一些精神性疾病的風險(例如，憂鬱症、創傷後壓力症候群等)。不同的個體在經歷壓力事件後所產生的壓力反應，具有高度的變異性，對於某些個體而言，暴露於急性或慢性的壓力後，會產生過度的精神性壓力反應，並最終造成精神疾病的發生。然而，值得注意的是，壓力通常伴隨著生物體恆定性的改變，此時需要適當的賀爾蒙分泌、心血管以及行為上的反應來協助個體整合生理以及心理狀態以維持體內恆定。然而對於中樞神經系統如何整合心理及生理狀態來產生壓力反應，目前的機轉仍不清楚。本研究的主要目的為：探討生理狀態的改變下，如何影響個體在經歷精神性壓力後的壓力反應。我們利用胞外電氣生理記錄的研究中發現，大鼠在水溫25°C經歷15分鐘強迫性游泳後，會促進海馬迴齒狀區長期增益現象的表現。然而，若將大鼠腎上腺切除或在壓力暴露前30分鐘投予礦物性皮質酮受體抑制劑RU28318，會分別抑制壓力促進長期增益現象的作用。在利用投MEK1/2 抑制劑 (U0126 或 PD98059) 的實驗中發現其具有抑制壓力促進長期增益的作用。此外，我們也觀察到皮下投予2.0 M鹽水造成大鼠高血鈉後，可有效的增加血漿中鈉離子濃度並且抑制壓力促進長期增益現象的作用，若將大鼠腎上腺切除，則可回復壓力促進長期增益現象的作用。進一步地，我們也發現單一的精神性壓力經驗會導致個體在下一次經歷相同壓力時，產生長期行為上的改變。綜合以上的發現，我們認為不同的生理狀態會影響個體在經歷精神性壓力後所產生的壓力反應，並且對於壓力記憶的形成具有影響。此等結果有助於我們瞭解個體間壓力感受程度的差異性。

Stressful life events increase the risk of developing psychopathology such as depression or post-traumatic stress disorder. Every individual experiences stressful life events, but shows a high degree of heterogeneity of responses. For some individuals, exposure to acute or chronic stress leads to a pathologically excessive response, and ultimately results in psychopathology. Importantly, stress often occurs within the context of homeostatic challenge, requiring integration of physiological and psychological needs into appropriate hormonal, cardiovascular and behavioral responses. However, the neural mechanisms underlying stress integration within the context of homeostatic adversity remain poorly understood. The objective of this proposal is to examine how physical state affects responding to psychogenic stressors. We found that experienced forced swimming stress (15 min in 25°C) enhanced long-term potentiation induction in the dentate gyrus of the rat hippocampus in vitro. The effect of stress on LTP was prevented when the animals were adrenalectomized or given mineralocorticoid receptor antagonist RU28318 before experiencing stress. Interestingly, the enhancing effect of stress on LTP was significantly ameliorated by treatment with MEK1/2 inhibitors, U0126 or PD98059, respectivity. In addition, we observed that hypernatremic challenge (2.0 M NaCl subcutaneous) can effectively elevate plasma sodium concentration and attenuate stress-induced enhancement of LTP, which was prevented by adrenalectomy. Furthermore, a single psychogenic stress experience also elicited a long-lasting consequence for future behavioral response to same stress. These results suggest that physical state affects responding to psychogenic stressors and stress memory formation, which underlies individual difference of stress sensitivity.

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