急性应激对大鼠脑内5-羟色胺1A受体mRNA表达的影响

目的 探讨急性应激对大鼠脑内5-羟色胺1A(5-HT1A)受体mRNA表达的影响。方法 将12只雄性Sprague-Dawley大鼠随机分为应激组和对照组,每组6只。根据5-HT1A受体互补DNA(eDNA)序列合成相应的特异性引物,用聚合酶链反应(PCR)法观察强迫游泳应激后3 h大鼠海马、下丘脑和中脑5-HT1A受体mRNA表达,并测定各脑区阳性电泳条带密度与β肌动蛋白(β-actin)密度的百分比。结果 应激后3 h,大鼠下丘脑5-HT1A受体mRNA表达相对水平为(64.3±6.7)％,显著低于对照组(78.9±8.7)％(t=3.263.P<0.05);海马、中脑5-HT1A受体mRNA表达相对水平分别为41.5％±7.1％、37.4％±5.6％,均分别显著低于对照组64.8％±9.6％、63.9％±6.3％(t分别为4.782、7.701,P均<0.01)。结论 急性应激后大鼠海马、下丘脑和中脑5-HT1A受体mRNA的表达降低。     

急性应激对大鼠脑内5-羟色胺2A受体mRNA表达的影响

目的　探讨急性应激对大鼠脑内 5 羟色胺 2A (5 HT2A)受体mRNA表达的影响。方法将 1 2只雄性Sprague Dawley大鼠随机分为应激组和对照组 ,每组 6只。根据 5 HT2A受体互补DNA(cDNA)序列合成相应的特异性引物 ,用聚合酶链反应 (PCR)方法观察强迫游泳应激后 3h大鼠海马、下丘脑和中脑 5 HT2A受体mRNA的表达 ,并测定各脑区阳性电泳条带密度与 β 肌动蛋白密度的百分比。结果　 (1 )应激组和对照组大鼠海马、下丘脑和中脑均存在 5 HT2A受体 (61 1bp)mRNA的表达 ;5 HT2A受体PCR产物序列与已知的 5 HT2A受体cDNA序列一致 ;(2 )应激组大鼠海马、下丘脑和中脑5 HT2A受体mRNA表达的相对水平分别为 (53± 5) %、(63± 8) %和 (47± 7) % ,均分别明显高于对照组[(42± 4) % ,(33± 6) %和 (2 7± 7) % ] ,t值分别为 4 .545 ,7.0 83 ,4.92 3 ,P均 <0 0 1。结论　急性应激后大鼠海马、下丘脑和中脑 5 HT2A受体mRNA的表达增多     

创伤后应激障碍大鼠海马组织5-HT1受体mRNA的表达

目的探讨创伤后应激障碍(posttraumatic stress disorder,PTSD)大鼠海马组织中5-羟色胺受体1mRNA的表达。方法随机将雄性Wistar大鼠分为对照组和PTSD组,采用改良的单一连续应激(SPS&S)方法刺激大鼠建立PTSD大鼠模型,Morris水迷宫实验检测大鼠记忆功能,化学发光法检测大鼠血清皮质醇浓度。建模后1d、4d、7d、14d分离海马组织,RT-PCR方法检测5-羟色胺受体1的变化。结果 (1)对照组水迷宫实验逃避潜伏期为(5.632±1.065)s,模型组为(20.762±3.236)s(t=9.932,P<0.01);(2)对照组血清皮质醇浓度为(1.25±0.12)μg/dl,模型组为(0.58±0.09)μg/dl(t=7.340,P<0.01);(3)应激后1d、4d、7d、14d海马5-HT1A受体mRNA表达相对水平分别为0.846±0.067、0.510±0.052、1.007±0.137、1.109±0.106,与对照组1.223±0.152相比较,1d、4d、7d表达低于对照组(P<0.05);5-羟色胺1受体其他亚型未见表达。结论 PTSD大鼠海马中5-HT1A受体mRNA表达降低。     

创伤后应激障碍大鼠海马组织5-HT1受体mRNA的表达

目的探讨创伤后应激障碍(Posttraumatic Stress Disorder,PTSD)大鼠海马组织中5-羟色胺受体1mRNA的表达。方法随机将雄性wistar大鼠分为对照组和PTSD组,采用SPS(single-prolonged stress)方法刺激大鼠建立PTSD大鼠模型,Morris水迷宫实验检测大鼠记忆功能,化学发光法检测大鼠血清皮质醇浓度。SPS刺激后1d、4d、7d、14d分离海马组织,RT-PCR方法检测5-羟色胺受体1的变化。结果 (1)对照组水迷宫实验逃避潜伏期为(5.632±1.065)s,模型组为(20.762±3.236)s(t=9.932,P0.01);(2)对照组血清皮质醇浓度为(1.25±0.12)μg/dl,模型组为(0.58±0.09)μg/dl(t=7.340,P0.01);(3)SPS刺激后1d、4d、7d、14d海马5-HT1A受体mRNA表达相对水平分别为0.846±0.067、0.510±0.052、1.007±0.137、1.109±0.106,与对照组相1.223±0.152比较,1d、4d、7d表达低于对照组(P0.05);5-羟色胺1受体其他亚型未见表达。结论 PTSD大鼠海马中5-HT1A受体mRNA表达降低。     

慢性应激大鼠中枢5-羟色胺含量及色氨酸羟化酶-2的表达变化

目的 探讨慢性不可预知轻度刺激（CUMS）大鼠模型中枢5-羟色胺（5-HT）含量和色氨酸羟化酶-2（TPH-2）的表达变化以及抗抑郁药的影响.方法 24只大鼠被随机分成3组,每组8只,A组为对照组,不给予刺激;B组为刺激不给药组,即CUMS应激鼠;C组为刺激给药组,即CUMS应激＋西酞普兰治疗组.实验为期6周,每周为大鼠称重,每3周测大鼠的糖水偏爱性,造模前后通过旷场试验评价大鼠行为,6周后对大鼠进行处死.处死后脑组织取样测定各脑区5-HT浓度及TPH-2 mRNA的表达水平.结果 经过6周干预,与A组比较,B组和C组体重明显降低（P＜0.05）;与A组及C组比较,B组糖水偏爱度显著降低（P＜0.05）,同时行为增多;B组5-HT浓度在海马中高于A组和C组,差异有统计学意义（P＜0.05）;在纹状体中,B组和C组5-HT浓度低于A组,差异有统计学意义（P＜0.05）;B组大鼠TPH2 mRNA在中缝核中表达低于A组,差异有统计学意义（P＜0.05）.结论 慢性应激可能引起中枢海马5-HT浓度增高及中缝核TPH-2表达降低,抗抑郁药可能引起中枢海马5-HT浓度降低,但未能影响中枢TPH-2的表达.     

大鼠大脑眶额叶区5-HT和5-HT1A受体与急性游泳应激性抑郁症

BACKGROUND： The orbitofrontal cortex （OFC） is a brain region closely associated with emotion. 5-hydroxytryptamine （5-HT） has been shown to be involved in human depression.
OBJECTIVE： To investigate OFC actions and mechanisms of 5-HT and 5-HT1A receptor （5-HT1AR） in stress-induced depression.
DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at Laboratory of Neurobiology, College of Life Science, Shaanxi Normal University between May 2006 and March 2008. MATERIALS： 5-HT, p-chlorophenylalanine （PCPA, an inhibitor to tryptophan hydroxylase） and spiperone （5-HT1AR antagonist） were provided by Sigma, USA; rabbit anti-rat 5-HT1AR antibody was provided by Tianjin Haoyang Biological Manufacture.
METHODS： A total of 40 male Sprague Dawley rats, aged 3 months, were randomly divided into five groups： control, model, 5-HT, spiperone ＋ 5-HT, and PCPA, with 8 rats in each group. Except for control group, rats in the other four groups were used to establish depression models by forced swimming for 15 minutes. At 30 minutes before forced swimming test, 0.5 pL of 5-HT （12.5 pg/pL）, PCPA （20 pg/pL）, spiperone （1.3 pg/pL） ＋ 5-HT （12.5 pg/pL, 10 minutes later）, and saline were respectively injected into the OFC of 5-HT, PCPA, spiperone ＋ 5-HT, and model groups, respectively. The control group received a saline microinjection into the OFC.
MAIN OUTCOME MEASURES： Forced swimming and open field tests were employed to measure animal behaviors, and immunohistochemistry was used to analyze 5-HT1AR expression in the OFC, cingulate cortex, and piriform cortex.
RESULTS： （1） Compared with the model group, 5-HT microinjection into the OFC prominently reduced immobility time in the forced swimming test and rearing in open field test （P 〈 0.05）; locomotion and grooming in open field test were increased, although there was no significance （P 〉 0.05）. Furthermore, following PCPA microinjection into the OFC （PCPA ＋ forced swimming stress）, immobility time in forced swimming test increased dramatically （P〈 0.01）, locomotion and rearing in open field test declined （P〈 0.05 and P 〈 0.01, respectively）. Compared with the 5-HT group, 5-HT1AR antagonist （spiperone ＋ 5-HT ＋ forced swimming stress） increased immobility time in forced swimming test （P 〈 0.01）, but decreased locomotion, rearing, and grooming in open field test. （2） Forced swimming stress markedly elevated 5-HT1AR expression in OFC, cingulate cortex, and piriform cortex （P〈 0.05 or P〈 0.01）.
CONCLUSION： 5-HT improved stress-induced depression, and 5-HT anti-depression effects are primarily achieved via 5-HT1AR. Stress-induced up regulation of 5-HT1AR expression might be a compensatory mechanism for decreased 5-HT expression.     

5-羟色胺转运体基因LPR及5-羟色胺1A受体C(-1019)G基因多态性的联合作用与重性抑郁症的关联研究

目的探讨5-羟色胺转运体基因LPR(5-HTT LPR)多态性和5-羟色胺1A受体(5-HT_(1A)R)C(-1019)G基因多态性的联合作用与重性抑郁症的关系。方法采用病例对照研究,以2005年10月-2007年5月在山西医科大学第一医院就诊的197例重性抑郁症患者为患者组,选取同期该院体检中心与患者组性别、年龄匹配的健康对照者197例为对照组。应用聚合酶链反应技术(PCR)、SDS-聚丙烯酰胺凝胶电泳(SDS-PAGE)及DNA直接测序法对两组的5-HTT LPR及5-HT_(1A)R C(-1019)G基因多态性进行检测。应用UNPHASED软件进行统计分析。结果患者组与对照组的5-HTT LPR和5-HT_(1A)R C(-1019)G多态性位点基因型及等位基因分布频率差异均无统计学意义(P均0.05)。多态性联合作用分析显示,患者组G-S等位基因组合频率高于对照组,差异有统计学意义(21.4%vs.12.4%,P=0.022)。结论在中国汉族人群中,5-HTT LPR和5-HT_(1A)R C(-1019)G的联合作用与重性抑郁症存在关联,G-S等位基因组合可能会增加重性抑郁症发病的危险性。     

5-HT1A受体的作用及其临床意义

5-羟色胺再摄取抑制剂（SSRI）是近十余年临床广泛应用的抗抑郁剂,有疗效好、不良反应轻和服药简便等多方面的优点,但在应用过程中也有起效较慢的缺点,特别是在抑郁症状严重需尽快解除时更显得不足。随着神经生理学和药理学的研究进展,人们已经发现SSRI类抗抑郁药起效慢的部份原因,并找到使其加快起效和疗效加强的一些措施。众所周知SSRI类抗抑郁药主要作用于中枢神经系统的5-羟色胺（5-HT）系统,抑制突触前膜对5-HT的再摄取、提高突触间隙的5-HT浓度是其主要药理作用机制。但抑郁症状的发生并非仅仅由于5-HT系统的功能不足所致,其中还包括去甲上腺素（NE）、多巴胺（DA）、γ-氨基丁酸（GABA）等系统的功能不足和／或紊乱,以及神经内分泌紊乱和受体后第二信使系统功能异常等多方面的因素。我们在本文中仅就5-HT1A受体的功能和5-HT1A激动剂和拮抗剂的药理作用和他们与SSRI疗效的关系进行综述。     

慢性应激抑郁大鼠脑内5-羟色胺受体mRNA表达

目的探讨慢性应激抑郁模型大鼠脑内前额叶、海马、中缝核、伏隔核5—羟色胺1A(5—HT1A)与5—羟色胺2A(5—HT2A)受体m RNA表达的变化。方法将成年雄性SD大鼠适应性喂养1w后随机分为实验组和对照组,每组10只。实验组连续28d,随机给予强迫游泳、夹尾、潮湿垫料、鼠笼倾斜、食物和水的剥夺等其中一种刺激,建立慢性轻度不可预知应激动物模型。对照组正常饲养,不予以实验性处理。采用旷场实验及糖水偏好实验评定其行为学改变;应用逆转录聚合酶链反应检测并比较两组大鼠大脑中前额叶、海马、中缝核、伏隔核5—HT1A与5—HT2A受体m RNA的表达水平。结果 1实验组5—HTl A受体m RNA表达在前额叶、海马、中缝核、伏隔核中分别为1.35±0.05、1.76±0.35、0.84±0.67、2.17±0.56,对照组分别为1.57±0.38、2.04±0.71、0.92±0.12、2.25±0.09。2组比较差异无统计学意义(P0.05);2实验组5—HT2A受体m RNA表达在前额叶、海马、中缝核、伏隔核中分别为1.24±0.80、0.37±0.75、0.34±0.14、0.45±0.41,对照组分别为1.66±0.43、2.02±0.12、1.90±0.56、1.28±0.31,2组比较在海马,中缝核,伏隔核中差异有统计学意义(P0.05)。结论 1慢性应激抑郁模型大鼠脑内前额叶、海马、中缝核、伏隔核中5—HT1A受体m RNA表达均无变化;2慢性应激抑郁模型大鼠脑内海马、中缝核、伏隔核中5—HT2A受体m RNA表达均减少;在前额叶表达无变化。     

改善精神分裂症认知障碍与5-羟色胺1A受体的关系研究进展

综述精神分裂症认知障碍与5-羟色胺1A受体间的关系。     

慢性不可预计温和应激大鼠microRNA差异表达谱分析

目的探讨慢性不可预计温和应激大鼠模型microRNA（miRNA）表达谱差异。方法采用慢性不可预计温和应激模型,将16只SD大鼠随机分为对照组和应激组,每组8只,对照组常规饲养,不予任何处理,应激组每天随机予1～2种温和刺激,共6周;造模结束后均采用旷场试验评价大鼠行为,安乐处死,取伏隔核低温保存。采用miRNA测序技术比较两组大鼠miRNA表达差异。结果与对照组比较,慢性不可预计温和应激大鼠有25个miRNA显著下调,2个miRNA显著上调。结论慢性不可预计温和应激可能使大鼠部分miRNA表达发生改变。     

艾司西酞普兰对慢性应激大鼠海马脑源性神经营养因子基因外显子表达及DNA甲基化的影响

目的 探讨艾司西酞普兰对成年慢性应激大鼠海马脑源性神经营养因子(BDNF)基因不同外显子表达及DNA甲基化的影响.方法 以慢性不可预测温和应激(chronic unpredictablemild stress,CUMS)建立应激抑郁模型并予艾司西酞普兰干预.56只雄性Sprague-Dawley大鼠随机分为CUMS+水组、CUMS+药组、对照+水组及对照+药组,每组14只,以蔗糖水偏好试验评估大鼠抑郁样行为;模型建立第3周后分别检测上述各组大鼠海马BDNF基因第Ⅰ、Ⅱ、Ⅳ、Ⅵ外显子mRNA及BDNF总mRNA(第Ⅸ外显子)表达和第Ⅳ启动子区DNA甲基化水平.结果 (1)蔗糖水偏好试验:模型建立第2,3周,CUMS+水组[(34±21)％,(63±21)％]蔗糖水偏好均低于对照+水组[(67±15)％,(80±15)％],差异均有统计学意义(事后检验,P均＜0.05);而CUMS+药组[(58士19)％,(80±14)％]与对照+水组间的差异均无统计学意义(事后检验,P均＞0.05).(2)BDNF外显子表达:模型建立第3周,第Ⅳ外显子mRNA为BDNF总mRNA(第Ⅸ外显子)表达中的最主要者.CUMS+水组BDNF第Ⅳ及Ⅸ外显子mRNA水平[(4.64±0.65)×10-3,(5.73±0.79) ×10-3]均低于对照+水组[ (6.14±0.87)×10-3,(6.82±0.35)×10-3],差异均有统计学意义(事后检验,P均＜0.05);而CUMS+药组[(5.69±0.18)×10-3,(6.91±0.98)×10-3]与对照+水组间的差异均无统计学意义(事后检验,P均＞0.05).(3)DNA甲基化:各组大鼠海马BDNF第Ⅳ启动子区DNA均未发生甲基化.结论 艾司西酞普兰主要调节BDNF第Ⅳ外显子转录阻止CUMS成年大鼠海马的该基因表达下降,艾司西酞普兰第Ⅳ启动子区DNA甲基化无影响.     

不同刺激参数rTMS对慢性不可预见应激大鼠行为的作用及大脑BDNF水平的影响

目的 观察不同刺激参数重复经颅磁刺激（rTMS）对慢性不可预见应激（CUS）模型大鼠行为学的作用,并观察其对大鼠脑源性神经营养因子（BDNF）水平的影响.方法 64只SD大鼠随机分为对照组（8只）、模型组（8只）和干预组（共6个亚组,每组8只）.对照组正常饲养21d后连续7d给予rTMS假刺激;模型组在造模后连续7d给予rTMS假刺激;干预组在造模后每天给予不同频率和强度的rTMS刺激,连续7d.实验期间观察大鼠体质量的变化,并采用运动箱和强迫游泳实验评估大鼠抑郁样行为,最后以酶联免疫吸附法测定大脑BDNF的水平.结果 （1）造模结束后,对照组大鼠的体质量、强迫游泳静止时间与其他两组相比均存在显著性差异（P＜0.01,P＜0.05）,而模型组和干预组大鼠比较没有上述差异（P＞ 0.05）.各组大鼠水平运动距离没有显著性差异（P＞0.05）.（2）rTMS干预后,①模型组大鼠的体质量显著低于对照组及干预组（5 Hz,0.84/1.26 T和10 Hz,0.84/1.26 T） （P ＜0.05）.②各组大鼠水平运动距离之间没有显著性差异;模型组强迫游泳静止时间百分比明显高于对照组及干预组（P＜0.05）.③模型组BDNF的水平低于对照组,而一定刺激条件的rTMS可以改善这一现象.④双因素方差分析显示,刺激频率可能是改善大鼠抑郁行为和调节BDNF的关键因素,而且5 Hz的抗抑郁效应更为显著.结论 不同刺激参数的rTMS对CUS动物抑郁行为的改善作用存在差异,大脑BDNF水平的变化可能参与了这一改善过程.     

Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice

Chronic psychological stress is one of the most important triggers and environmental risk factors for neuropsychiatric disorders. Chronic stress can influence all organs via the secretion of stress hormones, including glucocorticoids by the adrenal glands, which coordinate the stress response across the body. In the brain, glucocorticoid receptors (GR) are expressed by various cell types including microglia, which are its resident immune cells regulating stress-induced inflammatory processes. To study the roles of microglial GR under normal homeostatic conditions and following chronic stress, we generated a mouse model in which the GR gene is depleted in microglia specifically at adulthood to prevent developmental confounds. We first confirmed that microglia were depleted in GR in our model in males and females among the cingulate cortex and the hippocampus, both stress-sensitive brain regions. Then, cohorts of microglial-GR depleted and wild-type (WT) adult female mice were housed for 3 weeks in a standard or stressful condition, using a chronic unpredictable mild stress (CUMS) paradigm. CUMS induced stress-related behavior in both microglial-GR depleted and WT animals as demonstrated by a decrease of both saccharine preference and progressive ratio breakpoint. Nevertheless, the hippocampal microglial and neural mechanisms underlying the adaptation to stress occurred differently between the two genotypes. Upon CUMS exposure, microglial morphology was altered in the WT controls, without any apparent effect in microglial-GR depleted mice. Furthermore, in the standard environment condition, GR depleted-microglia showed increased expression of pro-inflammatory genes, and genes involved in microglial homeostatic functions (such as Trem2, Cx3cr1 and Mertk). On the contrary, in CUMS condition, GR depleted-microglia showed reduced expression levels of pro-inflammatory genes and increased neuroprotective as well as anti-inflammatory genes compared to WT-microglia. Moreover, in microglial-GR depleted mice, but not in WT mice, CUMS led to a significant reduction of CA1 long-term potentiation and paired-pulse ratio. Lastly, differences in adult hippocampal neurogenesis were observed between the genotypes during normal homeostatic conditions, with microglial-GR deficiency increasing the formation of newborn neurons in the dentate gyrus subgranular zone independently from stress exposure. Together, these findings indicate that, although the deletion of microglial GR did not prevent the animal’s ability to respond to stress, it contributed to modulating hippocampal functions in both standard and stressful conditions, notably by shaping the microglial response to chronic stress.     

慢性不可预见性温和应激后大鼠行为及海马细胞支架的改变

目的研究慢性不可预见性温和应激所致的动物行为学改变及细胞支架微管系统的动态性改变。方法将大鼠随机分为应激模型组（8只,以下简称模型组）和对照组（8只）,对模型组大鼠进行连续21d的慢性不可预见性应激。进行行为学观察,使用western blotting检测乙酰化微管蛋白（Acet—Tub）,酪氨酸微管蛋白（Tyr—Tub）。结果（1）模型组大鼠慢性应激后糖水偏好及自主活动显著减低,与对照组有显著差异;（2）模型组大鼠慢性应激后海马Acet—Tub表达升高,Tyr—Tub表达减低,与对照组有显著差异。结论慢性应激后微管动态性减低,神经可塑性受损。     

Increased expression level of corticotropin-releasing hormone in the amygdala and in the hypothalamus in rats exposed to chronic unpredictable mild stress

Objective

Corticotropin-releasing hormone (CRH) plays an important role in neuroendocrine, autonomic and behavioral responses to stressors. In the present study, the effect of chronic unpredictable mild stress (CUMS) on CRH neurons was investigated in rat brain.

Methods

The rats were exposed to one of the stressors each day for 21 d. Immunostaining was performed to detect the CRH-positive neurons in the paraventricular nucleus (PVN) of the hypothalamus and in amygdala.

Results

After the stress protocol, the animals showed a reduction in body weight gain as well as reduced sucrose preference and locomotor activity. Interestingly, the CRH neurons in both PVN and central nucleus of the amygdala (CeA) were stimulated by CUMS. The densities of CRH-containing neurons in both PVN and CeA were significantly higher than those in control group.

Conclusion

The CRH systems in PVN and CeA may both contribute to depression-like behaviors during CUMS.     

Brain monoamine receptors in a chronic unpredictable stress model in rats

Summary. Antidepressant drugs are devoid of mood-elevating effects in normal (non-depressed) human subjects, thus, it is necessary to evaluate the antidepressant property of compounds (drugs) in animal models of depression. Several animal models of depression have been introduced, however, only a few have been extensively validated. In the present study we report the results of investigations into monoaminergic receptors in the brain of rats subjected to chronic unpredictable stress (CUS) procedure (one of the well validated animal models of depression). We have examined the dopaminergic (D-1, D-2), adrenergic (α-1, β-1) and serotonergic (5HT-1A, 5HT-2A) receptors in different brain regions by a saturation radioligand binding method in rats subjected to CUS paradigm and control animals. CUS procedure resulted in a significant 29% increase in the D-1 receptor density in the limbic system and 52% increase of the density of 5HT-2A receptors in the cerebral cortex. The present data indicate that the increase of the density of brain D-1 and 5HT-2A receptors of rats subjected to CUS might be involved in the pathophysiology of "animal depression" (since chronic antidepressant treatment produced opposite changes i.e. decrease in the density of these receptors) and thus in pathophysiology of human depression. Received April 3, 2000; accepted August 17, 2000     

Peony glycosides produce antidepressant-like action in mice exposed to chronic unpredictable mild stress: Effects on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor

The root part of Paeonia lactiflora Pall. (Ranunculaceae), commonly known as peony, is a commonly used Chinese herb for the treatment of depression-like disorders. Previous studies in our laboratory have demonstrated that total glycosides of peony (TGP) produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to examine whether TGP could affect the chronic unpredictable mild stress (CUMS)-induced depression in mice. The mechanism(s) underlying the antidepressant-like action was investigated by measuring serum corticosterone level, glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) mRNA levels in brain tissues. CUMS, being lasted for 6 weeks, caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Whereas serum corticosterone level was significantly increased in mice exposed to CUMS, expressions of GR mRNA in hippocampus, and BDNF mRNA in hippocampus and frontal cortex, were decreased in CUMS-treated mice. Daily intragastric administration of TGP (80 or 160 mg/kg/day) during the six weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. The results suggest that the antidepressant-like action of TPG is likely mediated by modulating the function of hypothalamic-pituitary-adrenal axis and increasing the expression of BDNF in brain tissues.