系統識別號 U0026-2207201410450200
論文名稱(中文) 社會因素對於壓力反應及古柯鹼記憶的影響
論文名稱(英文) Impact of social factors on stress-produced responses and cocaine memory
校院名稱 成功大學
系所名稱(中) 基礎醫學研究所
系所名稱(英) Institute of Basic Medical Sciences
學年度 102
學期 2
出版年 103
研究生(中文) 曾文郁
研究生(英文) Wen-Yu Tzeng
學號 s58981167
學位類別 博士
語文別 英文
論文頁數 83頁
口試委員 指導教授-游一龍
中文關鍵字 早期神經新生  性別差異  荷爾蒙  社會互動  社會酬賞 
英文關鍵字 Early neurogenesis  Sex differences  Social interactions  Social reward 
中文摘要 社會因素對於壓力反應及藥物濫用扮演一個重要的角色。根據實驗室先前的研究發現,經歷一個壓力的程序時,有同種雄鼠的陪伴可以反轉壓力所引起齒狀回內神經新生的減少。這些發現意味著 1)小鼠齒狀回的神經新生可以被壓力所影響;2)同種動物的存在可以使用做為一個有效的社會支持方式,以減少某些壓力所引起的反應。一些研究顯示成年的公鼠與母鼠齒狀迴內表現不同程度的神經新生。壓力的易感性及某些情緒疾病是具有性別差異的。我的論文分成兩個部分。在第一個部分,我們決定使用動物模式去探討齒狀回神經新生的性別差異及性腺荷爾蒙對於壓力引起齒狀回神經新生下降的影響。我們企圖去檢驗陪伴抵抗壓力減少齒狀回神經新生所產生的保護作用,是否具有性別差異。此外,社會因素似乎會去影響藥物的使用及藥物的依賴性。因此,在第二部份我想去探討社會互動是否能調節古柯鹼所引發的場地制約偏好。我們具體假設社會互動能降低古柯鹼所引發的欣快感。我們使用古柯鹼制約場地偏好做為檢查古柯鹼引發欣快感的動物模式,來檢驗同種社交對於古柯鹼制約場地偏好強度的影響。第一部份的結果顯示,雌鼠及雄鼠齒狀回內新增生細胞及神經母細胞的基礎數目,以及壓力所改變分化成神經的細胞數目具有性別差異。此性別差異可能部份是由於兩種性別所分泌的性腺荷爾蒙不同所導致。雄鼠及雌鼠氣味可以藉由恢復大腦神經滋養因子及神經生長因子對雄鼠產生保護作用,以避免壓力所降低新增生細胞及神經母細胞。但對雌鼠則無此效果。在第二部分的結果顯示,同伴陪伴可能會藉由減少古柯鹼刺激伏隔核內多巴胺釋放,降低古柯鹼引發場地制約偏好。
英文摘要 Social factors play an important role in stress responses and drug abuse. Our previous report indicated that presence of male conspecifics throughout a stress procedure reversed the stress-induced decreases in dentate gyrus (DG) neurogenesis in male mice. These findings imply that 1) mouse DG neurogenesis is susceptible to stress and 2) presence of conspecifics can be used as an effective way of social support to attenuate certain stress-induced responses in mice. It was of interest to note that adult male and female animals exhibited differential degree of DG neurogenesis. Moreover, stress susceptibility and the prevalence of certain emotion disorders were variant in two sexes. This study was divided into two parts. First part was undertaken to assess sex differences and the modulating effects of gonad intactness and the estrous phase on basal and the stressor-decreased cell proliferation and early differentiation in Balb/C mouse dentate gyrus (DG). Besides, we compared the stress-reversing effects exerted by the presence of male and female Balb/C mouse odors in stressed male and female mouse DG in this regard. A number of social factors have been known to affect drug use and the development of drug dependence. Second part was undertaken to study whether the presence of a companion group may affect cocaine-produced hedonic effect by using cocaine-induced conditioned place preference (CPP) in a mouse model. Three male conspecific cocaine-free or -treated mice in together served as a conspecific mice served as a companion group in this study. In the first part, the results indicated that sexual differences in baselines in the number of newly proliferative cells, neuroblasts, and the sensitivity to stress-altered neuronal lineage commitment in the DG could be, in part, due to gonadal hormone differences between the two sexes. Mouse odors may reverse stressor-decreased newly proliferative cells and neuroblasts in male, but not in female, mouse DG by restoring BDNF and NGF levels. In the second part, the results indicated that the presence of companions may attenuate cocaine-produced CPP possibly by decreasing cocaine-stimulated dopamine release in the nucleus accumbens
論文目次 中文摘要 3
Abstract 4
誌謝 5
Table of Contents 6-7
Figures 8
Part I
I-1. Introduction 9-13
I-2. Materials and Methods 14-21
I-3. Results
I-3.1 Sexual differences in basal and the stressor-induced decreases in newly cell proliferation and early neuronal differentiation 22
I-3.2 Basal and the stressor-decreased newly cell proliferation and early neuronal differentiation in the DG in OVX and sham surgical female mice 23
I-3.3 Basal and the stressor-decreased new cell proliferation and early neuronal differentiation in the DG in female mice at estrous phases 25
I-3.4 Basal and the stressor-decreased newly cell proliferation and early neuronal differentiation in the DG in TX and sham male mice 26
I-3.5 The protective effects associated with the company of mouse odors throughout the stressor in two sexes 27
I-3.6 DG BDNF and NGF levels and the presence of male, female odors and the stressor 30
I-4. Discussion 32-37
I-5. Conclusions 38
I-6. Figures 39-46
I-7. References 47-52

Part II
II-1. Introduction 53-55
II-2. Materials and Methods 56-62
II-3. Results
II-3.1 The presence of saline-treated companions decreased experimental mice’ cocaine-induced CPP 63
II-3.2 The presence of cocaine-treated companions decreased experimental mice’ cocaine-induced CPP 64
II-3.3 The state-dependent learning did not contribute to the companions-decreased cocaine-induced CPP 65
II-3.4 The presence of companions did not affect the development of cocaine-produced sensitization in locomotor activity or rectal temperature 66
II-3.5 The presence of companions did not affect the cocaine-stimulated CORT secretion 67
II-3.6 The presence of decreased the magnitude of cocaine-induced CPP possibly by abolishing the cocaine-stimulated dopamine release 68
II-3.7 Cocaine pretreatment reverse the presence of saline-treated companions decreased experimental mice’ cocaine-induced CPP 69
II-4. Discussion 71-72
II-5. Conclusions 73
II-6. Figures 74-81
II-7. References 82-83
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