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1.
胡黄连苷Ⅱ对慢性应激抑郁大鼠的治疗作用及其机制 总被引:1,自引:1,他引:0
[摘要]目的观察胡黄连苷Ⅱ抗抑郁作用,探讨其作用机制。方法雄性SD大鼠96只,随机分为6组,每组16只。正常组、模型组给予等剂量0.9%氯化钠注射液,胡黄连苷Ⅱ低、中和高剂量组分别给予1,3,10 mg&;#8226;kg 1胡黄连苷Ⅱ,丙米嗪组给予15 mg&;#8226;kg 1 丙米嗪,腹腔注射给药,持续14 d。通过强迫游泳(FST)、敞箱实验(OFT)观察应激后各组大鼠行为学的变化。采用放射免疫方法检测大鼠血浆促肾上腺皮质激素(ACTH)和皮质酮(CORT)的水平。结果经慢性应激21 d后,模型组中FST不动时间增加,OFT水平与垂直得分下降,血浆ACTH、CORT含量增高,与正常组比较均差异有统计学意义(P<0.05)。经1,3,10 mg&;#8226;kg 1胡黄连苷Ⅱ和阳性对照药丙米嗪治疗14 d后,大鼠FST不动时间降低、OFT水平与垂直得分增高,血浆中ACTH、CORT含量降低,与模型组比较均差异有统计学意义(P<0.05)。结论胡黄连苷Ⅱ具有缓解抑郁模型行为学损伤的作用,其机制可能与其调节慢性应激大鼠血浆ACTH和CORT的水平有关。 相似文献
2.
目的研究小补心汤总黄酮(XBXT-2)对海马及前额皮质神经胶质细胞的影响。方法采用连续28 d每天给予大鼠1或2种不可预测的刺激建立慢性应激模型,同时每日单次ig给予XBXT-2 25和50 mg.kg-1。采用免疫组化方法观察大鼠海马齿状回颗粒下层、CA3区和前额皮质星形胶质细胞的影响。结果免疫组化结果表明,慢性应激大鼠海马齿状回颗粒下层、CA3区和前额皮质星形胶质细胞数目减少,形态萎缩,吸光度值显著降低(P<0.01)。伴随给予XBXT-2 25和50 mg.kg-1可显著逆转这一改变,吸光度值显著增加(P<0.01),阳性药丙米嗪具有同样的作用。结论 XBXT-2可逆转海马齿状回颗粒下层、CA3区和前额皮质星形胶质细胞的应激性损伤,这可能是其抗抑郁作用的重要细胞分子机制之一。 相似文献
3.
贯叶金丝桃粗提物的黄酮部位在强迫动物游泳实验(FST)中显示明显抗抑郁活性,该部位含金丝桃苷和异槲皮苷等。罗布麻Apocynum venetum L.叶水醇提取物含2.1%金丝桃苷和2.7%异槲皮苷,因而作者采用FST研究了该提取物的抗抑郁作用及活性成分。在急性给药方式实验中,40只雄性CD大鼠分为5组,第1组为对照组,服用去离子水,第2组口服丙咪嗪30mg/kg,第3~5组分别口服125、250和500mg/kg的罗布麻 相似文献
4.
小补心汤总黄酮提取物对慢性应激模型大鼠的抗抑郁作用 总被引:1,自引:0,他引:1
目的古代文献记载小补心汤(XBXT,由代赭石、旋覆花、竹叶和淡豆豉4味中药组成)有缓解抑郁情绪的作用。应用大鼠慢性应激模型探讨XBXT总黄酮(XBXT-2)的抗抑郁作用及可能机制。方法连续28d给予大鼠一系列慢性不可预测性的刺激建立慢性应激模型,同时给予XBXT-2(25或50mg·kg-1·d-1,ig)或丙米嗪(10mg·kg-1·d-1,ig),采用蔗糖饮水实验、开场活动实验和新奇抑制摄食实验观察抗抑郁行为效应;采用酶联免疫吸附实验检测血清皮质酮含量,Western蛋白印迹法检测海马糖皮质激素受体(GR)α/β、脑源性神经营养因子(BDNF)、磷酸化cAMP反应元件结合蛋白(p-CREB)、细胞外信号调节激酶(ERK1/2)及其磷酸化形式(p-ERK1/2)蛋白表达水平。结果XBXT-2或丙米嗪可逆转慢性应激大鼠蔗糖饮水偏嗜度降低、自发活动减少及新奇抑制摄食潜伏期延长,显著降低应激大鼠血清皮质酮含量,上调海马GRα/β,BDNF,p-CREB和p-ERK1/2蛋白表达。结论XBXT-2对慢性应激大鼠具有抗抑郁作用,其机制可能与抑制下丘脑-垂体-肾上腺轴的过度激活,上调海马BDNF相关的神经营养通路中蛋白表达有关。 相似文献
5.
目的:通过观察慢性应激对大鼠行为学的变化和海马与大脑皮层脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)及其受体酪氨酸激酶B(tyrosine kinase receptor,TrkB)表达的影响,探讨黄精总皂苷(saponins ofRhizoma Polygonati,SRP)抗抑郁作用及其机制。方法:48只SD大鼠,分为6组:正常组、模型组、氟西汀(fluoxetine,Flu)组(2 mg.kg-1)、SRP低、中、高剂量组(30,60,120 mg.kg-1)。采用不同应激因子交替持续应激21 d复制大鼠慢性应激抑郁模型,观察大鼠行为学指标和实验前后动物学习记忆能力等变化,用免疫组化法测定海马和大脑皮层中BDNF及TrkB的表达。结果:①应激刺激后,行为学指标显示,与正常组相比,模型组大鼠明显处于抑郁状态。②海马、大脑皮层可见到BDNF,TrkB染色阳性细胞,模型组阳性细胞数目及其灰度少于正常组和SRP低、中、高剂量组。结论:SRP能有效地减少慢性应急模型大鼠海马和大脑皮层神经元表达BDNF和TrkB的降低,SRP可能通过减少BDNF和TrkB的降低... 相似文献
6.
目的 比较度洛西汀与丙米嗪治疗抑郁症的疗效及不良反应. 方法 将58例符合CCMD-3抑郁症诊断标准的患者随机分为两组,治疗组30例,对照组28例. 治疗组给予度洛西汀,平均剂量(40.8±20.5) mg8226;d-1,po;对照组给予丙米嗪,平均剂量(158.1±16.5) mg8226;d-1,po;两组疗程均为6周. 采用汉密尔顿抑郁量表(HAMD)、不良反应量表(TESS)评定疗效及药品不良反应. 结果 治疗组有效率为77.8%,对照组有效率为76.9%. 两组疗效差异无显著性(P>0.05),治疗组起效快,且不良反应较对照组少. 结论 度洛西汀治疗抑郁症疗效好,起效快,不良反应轻. 相似文献
7.
《沈阳药科大学学报》2019,(5):421-426
目的为了探讨辣椒碱(capsaicin)抗小鼠抑郁样作用及其可能的作用机制。方法成年雄性小鼠每天1次灌胃辣椒碱,连续7 d。第7天给药后1 h进行强迫游泳实验(forced swimming test,FST)、悬尾实验(tail suspension test,TST)或旷场实验(open field test,OFT)。FST行为学实验结束后断头迅速取双侧海马、皮质前额叶。比色法和酶联免疫吸附法(ELISA)分别测定海马(hippocampus)及皮质前额叶(prefrontal cortex,PFC)中单胺氧化酶(monoamine oxidase,MAO)活性和5-羟色胺(5-hydroxytryptamine,5-HT)含量。结果辣椒碱显著缩短小鼠在FST和TST中的不动时间,但对OFT中的水平活动时间和活动距离均无明显影响;同时降低FST小鼠的海马和PFC中MAO活性,升高其5-HT含量。结论辣椒碱对小鼠可能有一定的抗抑郁样作用,其机制可能与抑制海马及皮质前额叶MAO活性、增加其5-HT神经递质含量有关。 相似文献
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目的研究常春藤皂苷元抗抑郁效果,探讨其药理作用,为研制新型抗抑郁药提供科学的理论依据。方法采用大鼠慢性不可预知温和应激(CUMS)建立外源性抑郁模型以及新生大鼠(8~21 d)注射氯丙咪嗪制备内源性抑郁模型。成功建立抑郁模型后随机分为空白对照组、模型组、西酞普兰5 mg·kg-1、常春藤皂苷元5 mg·kg-1组,连续28 d灌胃给药。给药结束后,分别进行旷场试验、糖水消耗实验、高架十字迷宫以及强迫游泳等实验评价药物的抗抑郁效果。结果在CUMS外源性抑郁模型中,给药两周后,阳性对照药西酞普兰起效效果较常春藤皂苷元快;连续给药4周后,常春藤皂苷元治疗组表现出明显的优势:在旷场实验中,常春藤皂苷元组大鼠的水平跑格数和直立次数与模型组相比有增加的趋势;在糖水消耗实验中,糖水偏爱度显著升高;在十字高架迷宫实验中,其在开臂区滞留时间百分比明显升高;在强迫游泳实验中,常春藤皂苷元大鼠的不动时间显著下降。而在内源性抑郁模型中,也观察到常春藤皂苷元在一定程度上改善抑郁大鼠的行为学表现。结论在两种抑郁模型中初步证实了常春藤皂苷元具有一定的抗抑郁作用,而这种抗抑郁作用是慢性起效的,其抗抑郁机制有待进一步研究。 相似文献
9.
目的 研究美沙拉嗪缓释剂对2,4,6 三硝基苯磺酸(2,4,6-trinitro picrylsulfonic acid,TNBS)诱导的溃疡性结肠炎肿瘤坏死因子α(tumor necrosis factor α,TNF-α)、白细胞介素(interleukin,IL) 1β、IL-6表达的影响,探讨美沙拉嗪缓释剂的抗炎机制. 方法 应用TNBS/乙醇建立大鼠溃疡性结肠炎模型,实验设正常对照组、模型组、药物治疗组(给予美沙拉嗪溶液100 mg8226;kg-18226;d-1), 阳性对照组(给予5-对氨基水杨酸100 mg8226;kg-18226;d-1),每组10只,每天灌胃2次,给药时间从造模后第1天开始至实验结束,共7 d,观察大鼠疾病活动指数(disease index,DAI)、体质量变化及结肠病理学改变,生化法检查大鼠结肠组织髓过氧化物酶(myeloperoxidase,MPO)活性,逆转录聚合酶链反应(Real-time PCR)检测肠组织TNF-α、IL-1β、IL-6mRNA的表达水平. 结果 与正常对照组比较,模型组大鼠结肠组织MPO活性及TNF-α、IL-1β、IL-6mRNA表达量明显增多(P<0.05).与模型组和阳性对照组比较,药物治疗组MPO活性及结肠组织TNF-α、IL-1β、IL-6mRNA的表达明显减少(P<0.05).模型组和阳性对照组差异无统计学意义. 结论 美沙拉嗪缓释剂对大鼠实验性溃疡性结肠炎具有治疗作用,其机制与通过降低中性粒细胞的浸润、抑制促炎因子TNF-α、IL-1β、IL-6mRNA等的表达有关. 相似文献
10.
舍曲林联合氯硝西泮治疗氯丙咪嗪无效的强迫症 总被引:1,自引:0,他引:1
目的: 探讨舍曲林联合氯硝西泮对氯丙咪嗪治疗无效的强迫症的疗效.方法: 对52例氯丙咪嗪治疗无效的强迫症住院患者随机分为治疗组和对照组各26例.治疗组给予舍曲林50 mg8226;d 1,3 d后增至100 mg8226;d 1,氯硝西泮4 mg8226;d 1,3 d后增至8 mg8226;d 1,均口服;对照组仅给予舍曲林,用法同治疗组.疗程均为8周.采用Yale Brow强迫量表(Y Bocs)和副作用量表(TESS)评定疗效和不良反应.结果: 治疗组显效率64.5%,对照组显效率38.5%;治疗第4,8周末Y Bocs评分治疗组优于对照组(P<0.05);不良反应两组差异无显著性(P>0.05).结论: 舍曲林并氯硝西泮治疗氯丙咪嗪无效的强迫症安全,有效. 相似文献
11.
Yang-Hee Jung Sa-Ik Hong Shi-Xun Ma Ji-Young Hwang Jun-Sup Kim Ju-Hyun Lee Jee-Yeon Seo Seok-Yong Lee Choon-Gon Jang 《Biomolecules & therapeutics.》2014,22(5):453-459
Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in mice that resembles some of the symptoms of human depression. In the present study, we used a chronic mild stress animal model of depression and anxiety to examine the responses of two strains of mice that have different behavioral responsiveness. An outbred ICR and an inbred C57BL/6 strain of mice were selected because they are widely used strains in behavioral tests. The results showed that the inbred C57BL/6 and outbred ICR mice were similarly responsive to CMS treatment in sucrose intake test (SIT) and open field test (OFT). However, the two strains showed quite different responses in forced swimming test (FST) and novelty-suppressed feeding (NSF) test after 3 weeks of CMS treatment. Only C57BL/6 mice displayed the depression- and anxiety-like behavioral effects in response to CMS treatment in FST and NSF test. Our results suggest that there are differences in responsiveness to CMS according to the different types of strain of mice and behavioral tests. Therefore, these results provide useful information for the selection of appropriate behavioral methods to test depression- and anxiety-like behaviors using CMS in ICR and C57BL/6 mice. 相似文献
12.
Long-lasting behavioral effects and recognition memory deficit induced by chronic mild stress in mice: effect of antidepressant treatment 总被引:2,自引:0,他引:2
Elizalde N Gil-Bea FJ Ramírez MJ Aisa B Lasheras B Del Rio J Tordera RM 《Psychopharmacology》2008,199(1):1-14
RATIONALE: Many studies support the validity of the chronic mild stress (CMS) model of depression in rodents. However, most of them focus on analysis of reactivity to rewards during the CMS and/or depressive-like behavior shortly after stress. In this study, we investigate acute and long-term effects of CMS and antidepressant treatment on depressive, anxiety-like behavior and learning. MATERIALS AND METHODS: Mice (C57BL/6) were exposed to CMS for 6 weeks and anhedonia was evaluated by weekly monitoring of sucrose intake. Paroxetine (10 mg kg(-1)day(-1) i.p.) or saline were administered the last 3 weeks of CMS and continued for 2 weeks thereafter. Behavioral tests were performed over the last week of CMS (acute effects) and 1 month later (long-term effects). RESULTS: Mice exposed to CMS displayed both acute and long-term decreased sucrose intake, increased immobility in the forced swimming test (FST) and impaired memory in the novel object recognition test. It is interesting to note that a correlation was found between the cognitive deficits and the helpless behavior in the FST induced by CMS. During the CMS procedure, paroxetine treatment reverted partially recognition memory impairment but failed to prevent the increased immobility in the FST. Moreover, it decreased on its own sucrose intake. Importantly, the long-term effects of CMS were partially prevented by chronic paroxetine. CONCLUSIONS: CMS leads to a long-term altered behavioral profile that could be partially reverted by chronic antidepressant treatment. This study brings novel features regarding the long-term effects of CMS and on the predictive validity of this depression animal model. 相似文献
13.
目的:研究左旋薄荷酮(MTN)的抗抑郁作用及可能机制。方法:以开野实验、强迫游泳实验、悬尾实验、糖水偏好实验对ICR小鼠进行行为学观察,探讨左旋薄荷酮对抑郁模型小鼠行为学的改善作用,同时检测小鼠血清皮质酮及皮质中糖皮质激素受体(GR)、脑源性神经营养因子(BDNF)含量的变化。结果:左旋薄荷酮15、30 mg·kg-1能显著缩短小鼠强迫游泳、悬尾不动时间,显著提高慢性不可预知温和刺激(CUMS)小鼠糖水偏好值,并能显著降低CUMS小鼠血清皮质酮含量、升高GR mRNA和BDNF的表达。结论:左旋薄荷酮具有抗抑郁作用,其抗抑郁机制可能与抑制下丘脑-垂体-肾上腺轴(HPA轴)过度活化、促进皮质BDNF的表达有关。 相似文献
14.
目的 观察藏药佐太的抗抑郁和抗焦虑作用,并探讨其可能作用机制。方法 1)初步评价实验:在小鼠ig给予6.07、60.70、303.49、606.97 mg/kg佐太14 d后,通过强迫游泳实验和开场实验初步评价佐太对抑郁和焦虑的影响,同时通过检测小鼠血清中5-羟色胺(5-HT)和去甲肾上腺素(NE)水平来探讨佐太产生影响的可能作用机制。2)不可预测性慢性温和应激模型(CUMS)实验:建立CUMS模型,ig给予6.07、60.70、606.97 mg/kg佐太后,通过小鼠体质量变化、糖水偏爱实验、小鼠悬尾实验、开场实验和埋珠实验评价佐太对CUMS模型小鼠的抗抑郁和抗焦虑作用,同时检测小鼠血清中皮质酮(CORT)、促肾上腺皮质激素(ACTH)和下丘脑中促肾上腺皮质激素释放激素(CRH)水平,测定佐太对CUMS模型小鼠下丘脑-垂体-肾上腺(HPA)轴的影响。结果 1)佐太能够显著减少小鼠强迫游泳实验中不动时间(6.07、60.70、303.49、606.97 mg/kg);增加小鼠在开场实验中中央区停留时间百分率(606.97 mg/kg)和中央区运动百分比(303.49、606.97 mg/kg);增加小鼠血清中5-HT(6.07、606.97 mg/kg)和NE(6.07、303.49、606.97 mg/kg)水平。2)CUMS实验中,与对照组比较,经过42 d CUMS慢性应激小鼠表现出明显的抑郁和焦虑样行为,包括糖水偏爱率的降低、悬尾不动时间显著增加、开场实验中运动时间、中央区域停留时间及运动距离的减少和周边区域运动距离的增加、埋珠实验中埋珠个数的增加。而ig给予佐太(6.07、60.70、606.97 mg/kg)能够显著改善CUMS模型引起的上述症状,并且佐太(6.07、60.70 mg/kg)能够显著降低CORT、ACTH和CRH水平,抑制CUMS模型引起的HPA轴亢进。结论 佐太具有一定的抗抑郁和抗焦虑作用,并且其作用机制可能与升高5-HT、NE水平和抑制HPA轴亢进有关。 相似文献
15.
Context: The leaves and roots of the Taraxacum officinale F. (Asteraceae) is widely used as traditional medicinal herb in Eastern Asian countries.Objective: In the present study, the antidepressant-like effects of the water extract of T. officinale (WETO) leaves and roots were investigated in mice using forced swimming test (FST), tail suspension test (TST) and open field test (OFT).Materials and methods: Effects of acute (1-day) and chronic treatments (14-days) with WETO (50, 100 and 200?mg/kg) on the behavioral changes in FST, TST and OFT, and the serum corticotrophin releasing factor (CRF), adrenocorticotropic hormone (ACTH) and corticosterone concentration were assessed in mice.Results: Chronic treatment (14-days) with WETO at the doses of 50, 100 and 200?mg/kg significantly decreased the immobility time in both FST (92.6, 85.1 and 77.4?s) and TST (84.8, 72.1 and 56.9?s). Acute treatment (1-day) with WETO at a dose of 200?mg/kg also markedly decreased the immobility time in both FST (81.7?s) and TST (73.2?s). However, all treatments did not affect the locomotor activity in the OFT. Moreover, FST induced a significant increase in serum CRF (5.8?ng/ml), ACTH (104.7?pg/ml) and corticosterone levels (37.3?ng/ml). Chronic treatment (14-days) with WETO decreased the serum CRF (200?mg/kg: 3.9?ng/ml) and corticosterone (50?mg/kg: 29.9?ng/ml; 100?mg/kg: 22.5?ng/ml; 200?mg/kg: 19.8?ng/ml) levels.Discussion and conclusion: These results clearly demonstrated the antidepressant effects of WETO in animal models of behavioral despair and suggested the mechanism involved in the neuroendocrine system. 相似文献
16.
The objective of the present study was to examine the effect of long-term management of insulin resistance and hyperglycemia on neurobehavioral deficits in db/db mice. In this study, 5-week-old db/db and lean control mice were fed with rosiglitazone (20 mg/kg/day) mixed or standard chow for a duration of 5 weeks. Mice were monitored weekly for blood glucose concentration. Five weeks after the onset of treatment, they were subjected to the forced swim test (FST), pre-pulse inhibition (PPI), open field test (OFT) and fear-potentiated startle (FPS) test to examine for depression, psychosis-like behavior, locomotor activity and emotional learning, respectively. Rosiglitazone normalized hyperglycemia and improved glucose tolerance. Rosiglitazone significantly reduced immobility time in the FST in db/db mice, suggesting an antidepressant-like effect. However, rosiglitazone failed to reverse disruption of PPI in db/db mice, indicating its ineffectiveness against psychosis-like behavior. In the OFT, rosiglitazone did not affect the activity of db/db mice, suggesting its antidepressant-like effect was independent of changes in locomotor activity. In the FPS test, db/db mice showed impaired emotional learning and rosiglitazone failed to correct it. In conclusion, long-term blood glucose management in type-2 diabetics may help to limit the co-occurrence of depression but not the psychotic symptoms and ability to cope with stress. 相似文献
17.
目的:研究阿魏酸钠能否改善慢性不可预知温和刺激(chronic unpredicted mild stress,CUMS)抑郁大鼠的抑郁样行为并探讨其机制。方法:将SD大鼠随机分为正常对照组、CUMS模型组、CUMS+氟西汀(10 mg· kg-1)组、CUMS+阿魏酸钠(50,100,150 mg· kg-1)组。采用慢性温和不可预知应激方法建立大鼠抑郁模型,造模完成后,连续灌胃给药21 d。旷场实验、糖水偏爱实验、强迫游泳实验检测大鼠的行为学变化;生物化学方法检测大鼠海马超氧化物歧化酶(superoxide dismutase,SOD)和过氧化氢酶(catalase,CAT)活性及活性氧(reactive oxygen species,ROS)含量。实时荧光定量PCR(q-PCR)法检测海马炎症因子IL-1β、TNF-α、PGE2及IL-10基因的mRNA转录水平;酶联免疫吸附试验检测海马炎症因子IL-1β、TNF-α、PGE2及IL-10含量的变化。结果:行为学检测结果显示,与正常对照组相比,旷场实验中模型组大鼠水平运动和垂直运动得分降低(P<0.01),糖水偏爱实验中糖水偏爱度显著下降(P<0.01),强迫游泳实验中不动时间明显延长(P<0.01);分子生物学检测结果显示,模型组大鼠海马内ROS含量显著升高(P<0.01),SOD和CAT的活性显著降低(P<0.01),海马IL-1β、TNF-α、PGE2和IL-10 mRNA和蛋白水平明显升高(P<0.05,P<0.01)。阿魏酸钠和氟西汀均能不同程度地改善CUMS诱导的上述改变。结论:阿魏酸钠能明显改善CUMS所致的大鼠抑郁样行为,其机制可能与降低海马氧化应激水平和改善炎症反应相关。 相似文献
18.
Recent studies have revealed diverse therapeutically interesting pharmacological properties of a standardized Hypericum perforatum extract (HpE) potentially useful for treatments of patients with metabolic and psychiatric disorders. Consequently, the presented experiments were designed to test usefulness of the extract for the treatment of comorbid conditions of mood disturbances and anxiety in diabetic rats. Type 2 diabetes mellitus was induced in overnight fasted rats by a single i.p. injection of streptozotocin (STZ; 65 mg/kg), 15 min after an i.p. injection of nicotinamide (120 mg/kg). HpE was administered orally (100 and 200 mg/kg b.w..) to diabetic animals for 14 days. Anxiolytic activity was evaluated using open-field exploration test (OFT) and elevated plus maze (EPM) test. Antidepressant activity was assessed using Porsolt's forced swim test (FST). Fasting blood glucose levels in different groups were analyzed on the 14th day. Diabetic rats showed significant increase in anxiety in OFT and EPM compared to non diabetic normal control rats. Diabetic rats treated with HpE have shown significant anxiolytic activity in OFT and EPM test. In FST, immobility period of vehicle treated diabetic rats was significantly increased (p < 0.05) compared to normal control rats. Treatment with HpE significantly decreased (p < 0.001) immobility period compared to vehicle treated diabetic control rats. HpE treatment significantly reduced elevated blood glucose levels in diabetic rats. The presented observations strongly suggest that HpE could be suitable alternative therapeutic option for prevention, as well as treatment, of comorbidities caused by, or associated with, depression, anxiety and diabetes. 相似文献
19.
Bombi Lee Bongjun Sur Sunoh Kwon Mijung Yeom Insop Shim Hyejung Lee Dae-Hyun Hahm 《Biomolecules & therapeutics.》2013,21(4):313-322
Previous studies have demonstrated that repeated administration of the exogenous stress hormone corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis and results in depression and anxiety. The current study sought to verify the impact of catechin (CTN) administration on chronic CORT-induced behavioral alterations using the forced swimming test (FST) and the elevated plus maze (EPM) test. Additionally, the effects of CTN on central noradrenergic systems were examined by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity in rat brains. Male rats received 10, 20, or 40 mg/kg CTN (i.p.) 1 h prior to a daily injection of CORT for 21 consecutive days. The activation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily CTN administration significantly decreased immobility in the FST, increased open-arm exploration in the EPM test, and significantly blocked increases of TH expression in the locus coeruleus (LC). It also significantly enhanced the total number of line crossing in the open-field test (OFT), while individual differences in locomotor activities between experimental groups were not observed in the OFT. Taken together, these findings indicate that the administration of CTN prior to high-dose exogenous CORT significantly improves helpless behaviors, possibly by modulating the central noradrenergic system in rats. Therefore, CTN may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression and anxiety disorders. 相似文献
20.
Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus 总被引:1,自引:0,他引:1
Jiang B Xiong Z Yang J Wang W Wang Y Hu ZL Wang F Chen JG 《British journal of pharmacology》2012,166(6):1872-1887
BACKGROUND AND PURPOSE Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients of Panax ginseng with little toxicity and has been shown to have neuroprotective effects. In this study, we investigated the antidepressant-like effect of Rg1 in models of depression in mice. EXPERIMENTAL APPROACH The effects of Rg1 were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Rg1 was also investigated in the chronic mild stress (CMS) mouse model of depression with imipramine as the positive control. Changes in hippocampal neurogenesis and spine density, the brain-derived neurotrophic factor (BDNF) signalling pathway, and serum corticosterone level after chronic stress and Rg1 treatment were then investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressive mechanisms of Rg1. KEY RESULTS Ginsenoside Rg1 exhibited antidepressant-like activity in the FST and TST in mice without affecting locomotor activity. It was also effective in the CMS model of depression. Furthermore, Rg1 up-regulated the BDNF signalling pathway in the hippocampus and down-regulated serum corticosterone level during the CMS procedure. In addition, Rg1 was able to reverse the decrease in dendritic spine density and hippocampal neurogenesis caused by CMS. However, Rg1 had no discernable effect on the monoaminergic system. CONCLUSIONS AND IMPLICATIONS Our results provide the first evidence that Rg1 has antidepressant activity via activation of the BDNF signalling pathway and up-regulation of hippocampal neurogenesis. 相似文献