2010-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/642538摘要：百憂解是一種常用的抗憂鬱劑，它藉由抑制血清張力素的回收，提高其濃度，而達到抗憂鬱的效果。許多婦女在孕程中，因憂鬱而求助於藥物，然而，百憂解可穿過胎盤進入胎兒體內。對這些胎兒而言，接觸百憂解是不可避免的，而過高的血清張力素，則可能不利於對神經的發育。在大腦發育的過程中，底板是一個出現得早，且持續參與大腦皮層的發育的結構。百憂解對此重要部位的影響，值得我們探討。本計畫中，我們想驗證： 1)百憂解對發育中之底板神經元有何影響？ 2)這些影響是否導因於過高的血清張力素濃度？為了回答這些問題，我們計畫執行以下三方面的實驗： 1)以自出生到出生後四天，連續接受百憂解注射的大白鼠為材料，探討其底板神經元之發育受百憂解的影響。 2)以正常鼠腦切片為材料，探討血清張力素對底板神經元之電生理特性的影響。 3)以初生鼠之腦片作組織培養，探討血清張力素對底板神經元之發育的影響及作用機制。本研究不僅幫助我們瞭解底板神經元的成長，及其在大腦皮層發育中的角色，也讓我們認識過高的血清張力素擾亂大腦發育的機制。許多抗憂鬱劑都提高腦內血清張力素的濃度，本研究結果也將提醒社會大眾及醫藥人員，應該更謹慎地使用抗憂鬱劑，尤其是用於懷孕的婦女。<br> Abstract: Fluoxetine, as known as Prozac, is a frequently used selective serotonin reuptake inhibitor(SSRI)-type antidepressant, which increases the brain serotonin level and helps treatingdepression. Given growing number of pregnant women experience depressive mood illness,the use of antidepressants in some pregnant depressive women is unavoidable. Sincefluoxetine can pass the blood-placenta-barrier, the developing fetuses are inescapable to thedrug. It is known that serotonin plays important roles in neural development; elevated brainserotonin level might disturb the developing nervous system of the fetus. Given the corticalsubplate is an early emerged structure important for the consequential cortical development,the vulnerability of developing subplate neurons (SPns) in fluoxetine-exposed young animalsis considered. In this project, we would like to test the following hypotheses: 1) if neonatalfluoxetine treatment alters the expression of neuronal markers, physiological properties andmorphological features in developing SPns? 2) if these changes are resulted from elevatedserotonin level? In order to test our hypotheses, three lines of experiments will be conducted. Wewill 1) study the development of SPns in fluoxetine-treated (P0-P4) prats, from P4 to P35; 2)examine the dose- and time-, age- and receptor subtype-specific effects of serotonin in acutebrain slices from normal rats of P4 to P35; and 3) explore the mechanism underlyingserotonin-induced SPn changes using a long-term organotypic brain slice culture system. Byconducting the proposed experiments, we should advance our knowledge of SPn developmentin biochemical, histological, morphological and physiological aspects and the roles of SPn inlater cortical development. Furthermore, combining in vivo and in vitro approaches, weshould also reveal the mechanisms underlying serotonin-induced abnormal corticaldevelopment. Since serotonin is the target of most antidepressants, our results are alsoimportant to the general public and medical personnel. The use of antidepressant particular inpregnant women should be more concerned.丘腦皮直徑　抗憂鬱藥物　大腦發育　血清素thalamocortical afferentpaired-pulse ratioantidepressantbrain development