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研究生:林禧岳
論文名稱:電刺激大鼠側韁核對區辨性低頻操作式制約行為的影響
論文名稱(外文):The effects of electrical stimulation in the lateral habenula on operant behavior maintained by the differential reinforcement of low-rate (DRL) schedule of reinforcement in the rat
指導教授:廖瑞銘廖瑞銘引用關係
學位類別:碩士
校院名稱:國立政治大學
系所名稱:神經科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
畢業學年度:100
語文別:英文
論文頁數:60
中文關鍵詞:深部大腦電刺激區辨性低頻操作式制約(DRL)行為側韁核多巴胺受體抑制劑正腎上腺素受體抑制劑
外文關鍵詞:deep brain stimulationdifferential reinforcement of low-rate responding behaviorlateral habenuladopamine receptor antagonistsnorepinephrine receptor antagonists
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透過神經科學的研究,對於大腦的行為功能已有一定的認識,不同於以往的認識,目前認為神經行為機制不只由單一腦區或單一神經化學系統所調控。深部大腦電刺激經常被用來研究特定腦區的行為功能。但是,深部大腦電刺激的作用機制仍然不清楚。最近幾年臨床研究發現,利用電刺激在側韁核成功的治療憂鬱症患者。然而,目前認為側韁核與多巴胺系統互為負回饋作用,共同參與在動機行為的酬賞反應中。本實驗室先前的研究顯示,破壞韁核造成區辨性低頻操作式制約行為 (簡稱DRL行為)學習的障礙,然而,電刺激在側韁核造成DRL行為表現的結果還是未知的。所以,本實驗主要以電刺激在側韁核觀察大鼠行為上的改變,探討側韁核在行為上參與的功能。實驗一的結果顯示電刺激在側韁核並不影響自發性運動能力,在不同電流強度的刺激下也不會影響。實驗二的結果顯示電刺激在側韁核造成DRL 15秒的行為有類安非他命效果之行為表現,在高頻率電刺激有較顯著類安非他命的效果。實驗三的結果顯示電刺激在側韁核造成DRL 15秒的行為之影響,會被多巴胺受體抑制劑所抵消,而單獨注射巴胺受體抑制劑並不影響DRL 15秒的行為。實驗四的結果顯示電刺激在側韁核造成DRL 15秒的行為之影響,不會被正腎上腺素受體抑制劑所抵消。實驗五的結果顯示電刺激在側韁核造成DRL 72秒的行為之影響並不如DRL 15秒的行為顯著。實驗六的結果顯示電刺激在側韁核並不會造成大鼠無法區辨酬賞的量。綜合而言,側韁核在動機行為的角色,是透過影響多巴胺系統造成行為的改變。
Behavioral function of the brain has been studied in neuroscience and progressively accumulated informative data to reveal the neurobehavioral mechanisms. It is now realized that those underlying mechanisms of behaviors is not as such simple as previous thought of limiting only in one locus of the brain or solely by one neurochemical system. The deep brain stimulation is usually used to study the behavioral function of specific brain regions. However, the mechanism of the deep brain stimulation is still unclear. The previous study has shown that electrical stimulation of the lateral habenula (LHb) successfully treated depression symptoms in the patients. It is proposed that an inhibitory role of LHb on the mibrain dopamine (DA) system which mediates the reward-related behavior. A previous study of this lab showed that lesion of habenula impaired the acquisition of differential reinforcement of low-rate responding (DRL) behavior. But, the effect of LHb stimulation on the DRL behavior is still unclear. To determine the functions of LHb involving in the behavior, the electrical stimulation was applied in LHb to observe the behavioral change of rats. The results of Experiment 1 showed that the LHb stimulation had no effect on locomotor activity. In Experiment 2, the LHb stimulation was shown to affect DRL 15-s behavior, which effects were similar to those affected by amphetamine. Experiment 3 showed that the DA receptor antagonists reversed the effects of LHb stimulation, while experiment 4 showed that norepinephrine (NE) receptor antagonists had no reversal effect on DRL 15-s behavior. In Experiment 5, the amphetamine-like behavior induced by LHb stimulation had subtle effects on DRL 72-s behavior. Experiment 6 showed that the LHb stimulation had no effect on a discrimination task. These data suggest that the LHb modulating DRL behavior is DA-dependent.
Contents
謝誌…………………………………………………………………………….Ⅰ
中文摘要……………………………………………………………………….Ⅱ
Abstract………………………………………………………………………..Ⅲ
Contents…………………………………………………………………........Ⅴ
List of Tables………………………………………………………………….Ⅶ
List of Figures…………………………………………………………..........Ⅷ
Introduction……………………………………………………………………01
The application of deep brain stimulation in clinical and pre-clinical studies.……………………………………………………………………...02
The lateral habenulal………………………………………………………03
The LHb and differential reinforcement of low-rate responding
behavior……………………………………………………………………..05
Aims and the rationale of this study……………………………………...07
Materials and Methods……………………………………………………....09
Animals……………………………………………………………………..09
Apparatus…………………………………………………………………..09
DRL operant behavior………………………………………………….09
Locomotor activity………………………………………………………10
DRL behavioral training………………………………………………..10
Discrimination task……………………………………………………...11
Surgery……………………………………………………………………..12
Electrode preparation and habenula stimulation……………………….12
Drugs………………………………………………………………………..13
Procedures…………………………………………………………………13
Experiment 1…………………………………………………………….13
Experiment 2…………………………………………………………….14
Experiment 3…………………………………………………………….15
Experiment 4…………………………………………………………….16
Experiment 5…………………………………………………………….17
Experiment 6…………………………………………………………….17
Histology……………………………………………………………………17
DRL behavioral data………………………………………………………18
Statistical analyses………………………………………………………..19
Results………………………………………………………………………...20
Experiment 1……………………………………………………………….20
Experiment 2……………………………………………………………….20
Experiment 3……………………………………………………………….21
Experiment 4……………………………………………………………….23
Experiment 5……………………………………………………………….24
Experiment 6……………………………………………………………….24
Discussion…………………………………………………………………….27
References……………………………………………………………………39

List of Tables
Table 1 The effects of lateral habenula (LHb) stimulation on DRL 72-s
Behavior (Experiment 5)………………………………………45
Table 2 Within-session analyses of the effects of lateral habenula (LHb) stimulation on a reward discrimination task (Experiment 6)…………………………………………………..46
Table 3 Number of choices made in each 10-trial block on discrimination task (Experiment 6)……………………………47


List of Figures
Figure 1 The electrode and brain stimulation in the rat……………….48
Figure 2 Histology of brain section with the LHb………………………49
Figure 3 The effects of electrical stimulation in LHb on locomotor activity (Experiment 1)…..………...…………………………50
Figure 4 The dose effects of amphetamine on the distance of locomotor activity (Experiment 1).……………...…………..51
Figure 5 The effects of LHb stimulation on DRL 15-s behavior as measured by the six dependent variables (Experiment 2).52
Figure 6 The effects of LHb stimulation on the MRE ratio of DRL-15 behavior (Experiment 2).…………………………………….53
Figure 7 The effects of SCH23390 and eticlopride on the alteration of DRL 15-s behavior induced by LHb stimulation as measured by the six dependent variables (Experiment 3).54
Figure 8 The effects of SCH23390 and eticlopride on the alteration of DRL 15-s behavior induced by LHb stimulation as measured by MRE ratio (Experiment 3)….………………..55
Figure 9 The effects of SCH23390 and eticlopride on DRL 15-s behavior, as measured by the six dependent variables (Experiment 3)……………………………………………..…56
Figure 10 The effects of SCH23390 and eticlopride on DRL 15-s behavior as measured by MRE ratio (Experiment 3).…...57
Figure 11 The effects of prazosin, yohimbine and propranolol on the alteration of DRL 15-s behavior induced by LHb stimulation, as measured by the six dependent variables (Experiment 4)……………………………………………………………….58
Figure 12 The effects of prazosin, yohimbine and propranolol on the alteration of DRL15-s behavior induced by LHb stimulation as measured by MRE ratio(Experiment 4).……………….59
Figure 13 The effects of electrical stimulation in LHb on a reward discrimination task, as measured by choice of large reward, omission rate and response latency(Experiment 6).…….60

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