【摘要】：目的：應(yīng)激事件是導(dǎo)致抑郁癥的重要因素之一，慢性不可預(yù)見性應(yīng)激動物模型被廣泛地運用于抑郁癥的相關(guān)研究之中。中樞單胺類神經(jīng)遞質(zhì)5-羥色胺（5-hydroxy tryptamine，5-HT）、去甲腎上腺素（norepinephrine，NE）、多巴胺（dopamine，DA）水平紊亂是抑郁癥發(fā)病機制中最重要的假說之一，其中，5-HT能神經(jīng)元大多起源于腦干的中縫背核（dorsal raphe nucleus，DRN），神經(jīng)末梢可投射到腦內(nèi)幾乎所有區(qū)域。大鼠前邊緣皮質(zhì)則與情緒、記憶、動機等行為有關(guān)，抑郁模型大鼠電刺激DRN后，前邊緣皮質(zhì)的5-HT分泌是否受到影響未見報道。本研究運用碳纖維電極測量技術(shù)，在體電刺激中縫背核，記錄大鼠前邊緣皮質(zhì)區(qū)的5-HT的釋放含量，來探討慢性不可預(yù)見性應(yīng)激模型大鼠中縫背核分泌的變化，深入認識抑郁癥的發(fā)病機制與5-HT系統(tǒng)的關(guān)系。 方法：建立慢性不可預(yù)見性應(yīng)激所致抑郁癥大鼠模型，20只雄性SD清潔級大鼠（180-200g）被隨機分為模型組和對照組，每組10只。模型組單籠飼養(yǎng)，對照組分在兩個大籠里飼養(yǎng)，每籠5只。模型組大鼠在21天內(nèi)接受7中不同的應(yīng)激，每天一種刺激，每種刺激出現(xiàn)3次，同種刺激不能連續(xù)出現(xiàn)，以確保動物對應(yīng)激源的不可預(yù)見性，對照組則正常飼養(yǎng)。同時在造模前、造模第十天和造模結(jié)束后進行曠場實驗和糖水消耗實驗。造模完成之后，應(yīng)用碳纖維電極技術(shù)在體記錄大鼠中縫背核的分泌量，在實際測量中我們記錄下5-HT信號的峰值、達峰時間和半衰期三個指標。 結(jié)果：在造模前，造模第十天以及造模后，分別對大鼠進行曠場實驗行為測試和1%蔗糖溶液消耗量測定。在曠場實驗評分中，造模結(jié)束后模型組大鼠明顯低于對照組（模型組：24.4±6.9次，n=10，對照組：66.6±12.0次，n=10，P0.001），1%蔗糖溶液消耗量測定中，造模結(jié)束后模型組大鼠的糖水消耗量和糖水偏愛百分比均明顯低于對照組（糖水消耗量：模型組3.1±2.5g，n=10，對照組：9.6±5.1g，n=10，P0.01；糖水偏愛百分比：模型組46.2±25.4%，n=10，對照組：67.3±15.0%，n=10，P0.05）。造模結(jié)束后模型組大鼠的體重明顯低于對照組（模型組274.2±21.3g，n=10，對照組：348.8±22.2g，n=10，，P0.001）。電刺激中縫背核，在前邊緣皮質(zhì)用碳纖維電極技術(shù)檢測神經(jīng)遞質(zhì)釋放的情況，記錄信號的三個參數(shù)，即峰值、達峰時間和半衰期。模型組大鼠（n=5）和對照組大鼠（n=8）的5-HT釋放的峰值、達峰時間和半衰期均無顯著性差異。給予正常對照大鼠腹腔注射5-HT2A受體拮抗劑ketanserin（2mg/kg）,正常對照組大鼠5-HT釋放的峰值明顯增大（用藥前：159.0±60.8pA，，用藥后：312.8±87.8pA，n=8，P0.05）。給予模型大鼠腹腔注射5-HT1A受體拮抗劑NAN-190（5mg/kg）,模型組大鼠5-HT信號沒有差異。 結(jié)論：慢性不可預(yù)見性應(yīng)激可以制作較為穩(wěn)定的抑郁癥動物模型。5-HT2A受體拮抗劑ketanserin能增加前邊緣皮質(zhì)5-羥色胺的釋放。
[Abstract]:Objective: stress event is one of the important factors leading to depression. Chronic unpredictable stress animal model has been widely used in the study of depression. The disorder of central monoamine neurotransmitters 5-hydroxytryptamine (5-hydroxy tryptamine,5-HT), norepinephrine (norepinephrine,NE) and dopamine (dopamine,DA) is one of the most important hypotheses in the pathogenesis of depression. Most of the 5-HT neurons originate from the dorsal raphe nucleus of the brain stem), and the nerve endings can be projected to almost all areas of the brain. The anterior marginal cortex of rats was related to emotion, memory, motivation and other behaviors. it was not reported whether the 5-HT secretion of anterior marginal cortex was affected after electrical stimulation of DRN in depression model rats. In this study, carbon fiber electrode technique was used to record the release of 5-HT from the anterior marginal cortex of rats by electrical stimulation of dorsal raphe nucleus in vivo, to explore the changes of secretion of dorsal raphe nucleus in rats with chronic unpredictable stress, and to further understand the relationship between the pathogenesis of depression and 5-HT system. Methods: the rat model of depression induced by chronic unpredictable stress was established. 20 male SD clean rats (180 g / 200 g) were randomly divided into model group (n = 10) and control group (n = 10). The model group was fed in a single cage, while the control group was divided into two large cages with 5 cages each. The rats in the model group received 7 different stresses within 21 days, one kind of stimulation per day, each stimulus appeared three times, the same kind of stimulation could not appear continuously, in order to ensure the unpredictability of the corresponding stimuli, the control group was raised normally. At the same time, the open field experiment and sugar water consumption experiment were carried out before and after the tenth day of modeling and after the end of modeling. After modeling, carbon fiber electrode technique was used to record the secretion of dorsal raphe nucleus in vivo. The peak value, peak time and half-life of 5-HT signal were recorded in the actual measurement. Results: the behavior of open field experiment and the consumption of 1% sucrose solution were measured before, 10 days and after modeling. In the open field test score, the rats in the model group were significantly lower than those in the control group (model group: 24.4 鹵6.9 times, n 鈮

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