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系統識別號 U0026-0812200915031818
論文名稱(中文) Sex Differences and the Impact of Gonadal Hormones on Fear Memory: the Roles of Testosterone in Fear-Potentiated Startle
論文名稱(英文) Sex Differences and the Impact of Gonadal Hormones on Fear Memory: the Roles of Testosterone in Fear-Potentiated Startle
校院名稱 成功大學
系所名稱(中) 行為醫學研究所
系所名稱(英) Institute of Behavioral Medicine
學年度 97
學期 1
出版年 98
研究生(中文) 蔡佳妏
研究生(英文) Chia-Wen Tsai
電子信箱 s8694107@mail.ncku.edu.tw
學號 s8694107
學位類別 碩士
語文別 英文
論文頁數 37頁
口試委員 指導教授-游一龍
口試委員-楊延光
口試委員-葉宗烈
中文關鍵字 恐懼記憶  性別差異 
英文關鍵字 Fear-Potentiated Startle (FPS)  testosterone  fear memory  gonadal hormones  sex differences 
學科別分類
中文摘要 據流行病理學的研究顯示,女性罹患焦慮相關疾患的比率幾乎為男性的兩倍之多。此意味著人類在面對壓力情境時,性荷爾蒙可能在易感脆弱性有某程度的調節弁遄C雖然釵h研究顯示在盛行率上存在著性別差異,但此恐懼記憶的性別差異在動物實驗研究及背後機制研究並不多。本篇研究之目的:探討恐懼記憶的性別差異,及雄性荷爾蒙在腦區調控恐懼反應的形成和削弱之角色。在研究方法上,讓雌雄老鼠分別經歷光和電擊的配對以試圖建立恐懼記憶後,之後再給予兩回合的削弱程序(僅出現光刺激),分別記錄不同階段的恐懼反應。接著,在分開不同的組別給予單純性腺摘除、摘除後從周邊給予雌性或雄性荷爾蒙、以及在不同腦區注射雄性荷爾蒙等處理,以探討其對恐懼反應的表現及削弱情形。我們研究發現:(1) 未經過任何處理的雌老鼠,其恐懼反應程度明顯高於雄老鼠。 (2) 在性腺摘除後,雌鼠的反應差異不大;但雄鼠能減緩此差易情形。當進一步周邊給予性荷爾蒙後,恐懼反應趨勢又回到相似於一般正常組。 (3) 腦區注射雄性荷爾蒙能降低恐懼反應的表現,並持續到之後的暴露情境。因此我們推論,對恐懼記憶的形成及遺忘過程所存在的性別差異,雄性荷爾蒙在此可能具有某重要程度的調控作用。
英文摘要 An obvious sexual difference in anxiety disorders has been documented with a prevalence of 2 fold higher in women than it in men. Such sexual difference implies the roles of sex hormones in modulating the differential susceptibility to stress in two sexes. Although the sex-dependent prevalence rate has been consistently reported greater in women than in men, the specific roles of sex hormones on fear memory formation and extinction remained scarcely explored in animal models. This study was undertaken to examine the sexual differences in fear memory and the roles of testosterone in central anatomical substrates in mediating such sex differences by utilizing fear potentiated startle (FPS) paradigm in a rat model. Male and female rats were first accustomed to the constraint chamber in the dark and their startle responses were recorded then for the sporadic tone presentation (95dB). Our fear conditioning protocol consisted of an episode of 10-trial light-foot shock pairings. Three consecutive days (30 trials/day) of light alone presentation served as one bout of the extinction protocol. A total of two bouts of extinction protocol were used. Bilateral gonadectomy, systemic estradiol and testosterone supplement, and intra-accumbal injection of gonadal hormones were used in appropriate groups. We found that female rats exhibited greater fear potentiated startle responses in the acquisition test and lesser degree of extinction after the second bout of the extinction protocol as compared to male rats. We further demonstrated that ovariectomized rats displayed similar fear potentiated startle acquisition and extinction as the intact female rats, while orchidectomized rats displayed greater degree of fear-potentiated startle responses and more resistant to the extinction protocol as compared to the intact male rats. Finally, intra-accumbal testosterone infusion was found to effectively reverse such sensitized potentiated startle responses and resistance to extinction. We conclude that testosterone may play a pivotal role in determining the sexual differences of fear memory acquisition and forgetting process.
論文目次 Abstract…………………………………………………………………3
中文摘要…………………………………………………………………5
Contents…………………………………………………………………6
Introduction……………………………………………………………9
Materials and methods
1. Animals……………………………………………………………12
2. Gonadectomy and cyclic estradiol and testosterone
supplement…………………………………………………………12
3. Stereotaxic surgery and cannula implantation……………12
4. Microinjection procedure………………………………………13
5. Apparatus…………………………………………………………14
6. Acquisition and extinction of fear-potentiated startle
(FPS)………………………………………………………………15
7. Statistical analysis……………………………………………16
Results
1. Sexual difference in acquisition and extinction of FPS
were existed………………………………………………………17
2. The gonad removal reversed the sexual differences in
the acquisition and extinction of FPS……………………18
3. Estradiol supplement reversed the acquisition and
extinction of FPS………………………………………………20
4. Estradiol replacement facilitates FPS in Sprague Dawley
strain………………………………………………………………21
5. Testosterone supplement reversed the acquisition and
extinction of FPS.………………………………………………21
6. The FPS ratio did not be affect via the amplitude of
noise………………………………………………………………23
7. Microinjection of testosterone into CeA reduces
acquisition of FPS………………………………………………24
8. Microinjection of testosterone into BLA decreased
slightly formation of FPS……………………………………25
9. Microinjection of testosterone into BNST did not reverse
such sensitized potentiated startle responses…………26
10. DMSO, as dissolution in this study, did not affect the
FPS…………………………………………………………………26
Discussion……………………………………………………………28
Conclusions……………………………………………………………32
References……………………………………………………………33
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