慢性不可预见性应激模型大鼠中缝背核分泌的研究
发布时间：2019-06-20 04:24
【摘要】：目的：应激事件是导致抑郁症的重要因素之一，慢性不可预见性应激动物模型被广泛地运用于抑郁症的相关研究之中。中枢单胺类神经递质5-羟色胺（5-hydroxy tryptamine，5-HT）、去甲肾上腺素（norepinephrine，NE）、多巴胺（dopamine，DA）水平紊乱是抑郁症发病机制中最重要的假说之一，其中，5-HT能神经元大多起源于脑干的中缝背核（dorsal raphe nucleus，DRN），神经末梢可投射到脑内几乎所有区域。大鼠前边缘皮质则与情绪、记忆、动机等行为有关，抑郁模型大鼠电刺激DRN后，前边缘皮质的5-HT分泌是否受到影响未见报道。本研究运用碳纤维电极测量技术，在体电刺激中缝背核，记录大鼠前边缘皮质区的5-HT的释放含量，来探讨慢性不可预见性应激模型大鼠中缝背核分泌的变化，深入认识抑郁症的发病机制与5-HT系统的关系。 方法：建立慢性不可预见性应激所致抑郁症大鼠模型，20只雄性SD清洁级大鼠（180-200g）被随机分为模型组和对照组，每组10只。模型组单笼饲养，对照组分在两个大笼里饲养，每笼5只。模型组大鼠在21天内接受7中不同的应激，每天一种刺激，每种刺激出现3次，同种刺激不能连续出现，以确保动物对应激源的不可预见性，对照组则正常饲养。同时在造模前、造模第十天和造模结束后进行旷场实验和糖水消耗实验。造模完成之后，应用碳纤维电极技术在体记录大鼠中缝背核的分泌量，在实际测量中我们记录下5-HT信号的峰值、达峰时间和半衰期三个指标。 结果：在造模前，造模第十天以及造模后，分别对大鼠进行旷场实验行为测试和1%蔗糖溶液消耗量测定。在旷场实验评分中，造模结束后模型组大鼠明显低于对照组（模型组：24.4±6.9次，n=10，对照组：66.6±12.0次，n=10，P0.001），1%蔗糖溶液消耗量测定中，造模结束后模型组大鼠的糖水消耗量和糖水偏爱百分比均明显低于对照组（糖水消耗量：模型组3.1±2.5g，n=10，对照组：9.6±5.1g，n=10，P0.01；糖水偏爱百分比：模型组46.2±25.4%，n=10，对照组：67.3±15.0%，n=10，P0.05）。造模结束后模型组大鼠的体重明显低于对照组（模型组274.2±21.3g，n=10，对照组：348.8±22.2g，n=10，，P0.001）。电刺激中缝背核，在前边缘皮质用碳纤维电极技术检测神经递质释放的情况，记录信号的三个参数，即峰值、达峰时间和半衰期。模型组大鼠（n=5）和对照组大鼠（n=8）的5-HT释放的峰值、达峰时间和半衰期均无显著性差异。给予正常对照大鼠腹腔注射5-HT2A受体拮抗剂ketanserin（2mg/kg）,正常对照组大鼠5-HT释放的峰值明显增大（用药前：159.0±60.8pA，，用药后：312.8±87.8pA，n=8，P0.05）。给予模型大鼠腹腔注射5-HT1A受体拮抗剂NAN-190（5mg/kg）,模型组大鼠5-HT信号没有差异。 结论：慢性不可预见性应激可以制作较为稳定的抑郁症动物模型。5-HT2A受体拮抗剂ketanserin能增加前边缘皮质5-羟色胺的释放。
[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 卤6.9 times, n 鈮
本文编号：2502923
[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 卤6.9 times, n 鈮
本文编号：2502923
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