臺灣博碩士論文加值系統

中文摘要
本實驗使用體內微量透析技術 (in vivo microdialysis) 在麻醉的大白鼠探討活化內前額皮質區 (medial prefrontal cortex；mPFC) D2接受器 (receptor) 是否會調控積核 (nucleus accumbens；NAC) 多巴胺 (dopamine) 的釋放，而調控的機轉是否是經由皮質腹側被蓋麩胺酸神經 (cortical-ventral tegmental glutamatergic neuron) 來調控積核多巴胺的釋出。
在內前額皮質區灌流 D2 接受器作用劑 (agonist) quinpirole 100 uM (而非 1 uM 或 0.01 uM) 觀察到腹側被蓋區細胞外液麩胺酸 (glutamate) 的濃度 (67.2±6.3 %) 和積核多巴胺的濃度 (80.5±4.3 %) 有下降的情形。而灌流另一種 D2 接受器作用劑 quinelorane (0.01 uM, 1 uM, 100 uM) 也同樣觀察到腹側被蓋區細胞外液麩胺酸的濃度 (分別是：64.9±5.9 %, 60.1± 2.6 %, 71.6±4.0 %) 和積核細胞外液多巴胺的濃度 (分別是：71.1±2.7 %, 73.3±1.6 %, 65.1±2.6 %) 有下降的現象，但並沒有劑量相關性 (dose-dependent)。
在內前額皮質區單獨灌流 g-胺基酪酸 (GABA) GABAA接受器拮抗劑 (antagonist) bicuculline 50 uM 時，觀察到腹側被蓋區細胞外液麩胺酸上升至 145.0±3.3 %，而積核細胞外液多巴胺卻不受影響 (106.8±0.6 %)。然而，預先在內前額皮質區灌流 100 uM的 quinpirole 或 quinelorane，觀察到腹側被蓋區細胞外液麩胺酸原本下降的現象 (73.3±4.3 %, 68.4±2.8 %) 會因為共同灌流 bicuculline 50 uM 後，使得腹側被蓋區細胞外液麩胺酸的濃度下降情形有被拮抗的作用 (170.2±17.3 %, 100.0±4.0 %)。而積核細胞外液多巴胺在共同灌流 bicuculline 50 uM 前 (82.7±3.1 %, 57.9±5.2 %) 或共同灌流後 (71.3±1.5 %, 51.0±3.6 %) 都維持在下降的狀態。
由以上的實驗結果推測：(1) 在內前額皮質區中活化 D2 接受器同時對於腹側被蓋區麩胺酸和積核多巴胺有抑制性的調控，並且 (2) 活化內前額皮質區D2 接受器造成腹側被蓋區麩胺酸下降可能是透過內前額皮質區GABAA 接受器的神經傳導而來。(3) 在內前額皮質區共同灌流D2 接受器作用劑和 bicuculline 造成積核多巴胺仍然下降，可能是由於啟動了一個神經迴路：活化了皮質積核路徑進一步活化由積核投射到腹側被蓋區的 g-胺基酪酸神經，再對於中邊緣路徑產生抑制性調。

ABSTRACT
This study was designed to investigate whether activation of D2 receptor in the medial prefrontal cortex (mPFC) control the basal release of dopamine in the nucleus accumbens (NAC) and whether this control is mediated by glutamatergic afferents to the ventral tegmental area (VTA) by in vivo microdialysis in chloral-hydrate anaesthetized rats.
Local infusion of 100 uM (but not 1 uM or 0.01 uM) D2 receptor agonist quinpirole into the mPFC significantly decreased extracellular glutamate (67.2±6.3 % of baseline) in the VTA and dopamine (80.5±4.3 % of baseline) in the NAC. Infusion of another D2 receptor agonist quinelorane 0.01 uM, 1 uM and 100 uM into the mPFC also decreased extracellular glutamate (64.9±5.9 %, 60.1± 2.6 % and 71.6±4.0 %, respectively) in the VTA and dopamine (71.1±2.7 %, 73.3±1.6 % and 65.1±2.6 %, respectively) in the NAC, but the changes of glutamate in the VTA and dopamine in the NAC did not have does-dependent.
Local infusion of bicuculline (GABAA receptor antagonist) 50 uM into the mPFC alone increased the extracellular glutamate (145.0±3.3 %) in the VTA, but did not change the extracellular dopamine (106.8±0.6 %) in the NAC. Pretreatment with 100 uM quinpirole or quinelorane into the mPFC observed the decrease of glutamate in the VTA (73.3±4.3 %, 68.4±2.8 %) were blocked by after coadministration of bicuculline 50 uM into the mPFC, reversed the decrease of glutamate (170.2 ± 17.3 %, 100.0 ± 4.0 % respectively) in the VTA. Nevertheless, the dopamine in the NAC still decreased before (82.7±3.1 %, 57.9±5.2 %) or after (71.3±1.5 %, 51.0±3.6 %) coadministration bicuculline 50 uM into the mPFC.
Taken together, these results indicated that activation of D2 receptors in the mPFC (1) could inhibit the release of glutamate in the VTA and the release of dopamine in the NAC, simultaneously, and (2) decreased the glutamate in the VTA is through the neurotransmission of GABAA receptors in the mPFC. On the other hand, (3) the dopamine lowering of NAC caused by co-infusion D2 agonists and bicuculline is possible due to hypothetically creates a neuronal circuit in activating the cortical-accumbens pathway leading to the activation of GABA neuron from NAC to VTA resulting to inhibit the mesolimbic pathway.

目錄
1.中文摘要………………………………….1
2.英文摘要………………………………….3
3.緒論..……………………………….……5
4.實驗動機….………………………….….16
5.實驗設計……………………………..….20
6.實驗材料…………………………….…..21
7.實驗方法…………………………….…..27
8.組織切片確認…………………….……..28
9.統計方法………………………….……..29
10.實驗步驟與實驗流程………….……...30
11.實驗結果………………………….…...33
12.討論………………………………….….40
13.結論……………………………………..49
14.未來研究方向…………………………..50
15.圖表…………………………………....53
16.參考文獻………………………………..73

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