臺灣博碩士論文加值系統

許多證據支持古柯鹼強化成癮及繼續使用的行為是因為單胺類神經傳導素的釋放改變的假說。古柯鹼會阻斷這些神經傳導素經由轉運子回收收到突觸前的神經元，造成突觸間的神經傳導素的增加，進而引發強烈愉悅的感覺及造成取藥成癮的行為。之前有些研究顯示使用單胺類神經傳導素轉運子的抑制劑無法抑制古柯鹼的再次上癮。在本研究中，我們使用單胺類氧化酶B型基因剔除老鼠及長期給予單胺類氧化酶抑制劑去觀察古柯鹼的自我注射行為。我們發現1.慢性使用單胺類氧化酶抑制劑不會造成獲取自然酬賞物－食物的行為，但是會降低老鼠對於古柯鹼的愉悅感受及需求；2.單胺類氧化酶B型基因剔除老鼠比其基因對照型老鼠有較高古柯鹼的需求。

A large body of evidence supports the hypothesis that monoamines are involved in the cocaine craving and associated behavior. Cocaine has been known to block reuptake of these neurotransmitters by inhibiting their own transporters, thus enhance synaptic availability of these neurotransmitters. Increased synaptic monoamine concentration have been associated with the euphoric (reinforcing) efficacy and the priming effects of cocaine in reinstatement designs. In this study, the acquisition curve of cocaine self administration was examined in MAO subtype B knockout mice and long-term MAO inhibitor-treated mice. We found that 1) chronic MAO inhibitor (MAOI) treatment did not seem to affect the natural reward (food)-associated operant conditioning, while attenuated the rewarding effects of cocaine; 2) the responses for cocaine self administration in MAO subtype B knockout mice were higher than them in the wild type mice, however there was a similar acquisition curve for the food reward in knockout and wild type mice.

I. 摘要．．．．．．．．．．．．．． 1
II. Abstract．．．． 2
III. Key Words．．．．．．．．．．．．． 3
IV. Acknowledgments．．．．．．．．． 3
V. Aim．．．．．． 4
VI. Contents．．．．． 5-6
VII. Figure Index．．．．．．．．． 7
VIII. Context．．．．． 8-39
1. Introduction．．．． 8-9
2. Materials and Method．．．．．．．．．．． 10-20
2.1 Animals．．． 10
2.2 PCR．．．． 11
2.3 Drug．．． 12
2.4 Food and cocaine provided device．．．． 13
2.5 Locomotor Activity Measurement ．．．． 14
2.6 Elevated Plus Maze．．．．．．．．．．． 15
2.7 Resident-intruder Test．．．．．． 16
2.8 Food Training under the FR-1 Schedule．．．．．．．．．．．．．．． 17
2.9 Cocaine Self-administration Behavior under the FR-1 Schedule．．．．． 18
2.10 HPLC ．．． 19
2.11 Statistical analysis．．．．．． 20
3. Results．．．．． 21-32
3.1 PCR of the wild type mice and MAO subtype B knockout mice．．．．． 21
3.2 The dose response curve of monoamine oxidase inhibitor on locomotor activity．．．．．． 22
3.3 Impact of chronic MAOIs treatment on food training under the FR-1 schedules．．．．． 23
3.4 MAO subtype B mice and Wild type mice on food training under the FR-1 schedules．．． 24
3.5 Impact of chronic MAOIs treatment on cocaine self administration under the FR-1 schedules．． 25
3.6 MAO subtype B mice and Wild type mice on cocaine self administration under the FR-1 schedules．．． 26
3.7 MAO subtype B mice and Wild type mice on elevated plus maze．．．． 27
3.8 MAO subtype B mice and Wild type mice on resident-intruder．．．．． 28
3.9 DA levels in PFC, Striatum, NAc, and Hippocampus of MAO subtype B mice and Wild type mice．．．．．．．．．．．．．．．．．．．．．．． 29
3.10 DOPAC levels in PFC, Striatum, NAc, and Hippocampus of MAO subtype B mice and Wild type mice．．．．．．．．．．．．．．．．．．． 30
3.11 5-HT levels in PFC, Striatum, NAc, and Hippocampus of MAO subtype B mice and Wild type mice．．．．．．．．．．．．．．．．．．．．．． 31
3.12 5-HIAA levels in PFC, Striatum, NAc, and Hippocampus of MAO subtype B mice and Wild type mice．．．．．．．．．．．．．．．．．．． 32
4. Discussions．．． 33-34
5. Conclusions．．． 35
6. References ．．．． 36-39
IX. Appendix．．．．． 40-43

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