豆腐果苷抗抑郁作用的初步研究

目的初步探讨豆腐果苷的抗抑郁作用。方法采用小鼠悬尾实验及小鼠强迫游泳实验方法观察豆腐果苷的抗抑郁作用。结果在小鼠悬尾实验和小鼠强迫游泳实验中,豆腐果苷在20、30mg/kg剂量下能明显缩短小鼠的悬尾不动时间,在30、40mg/kg剂量下能明显缩短小鼠强迫游泳的不动时间。结论豆腐果苷在“行为绝望”动物模型中呈现抗抑郁作用,且量效曲线呈现行为学特有的U型曲线特征。     

越鞠丸及各单味药醇提物对小鼠的抗抑郁作用研究

目的:探讨越鞠丸全方及各单味药(香附、川芎、栀子、苍术、神曲)醇提物的抗抑郁活性。方法:采用小鼠悬尾和强迫小鼠游泳实验2种行为绝望法复制小鼠抑郁模型,对越鞠丸全方及各单味药分别进行抗抑郁活性研究。结果:除神曲外,越鞠丸全方及各单味药醇提物均能不同程度地缩短小鼠悬尾不动时间和小鼠强迫游泳不动时间,具有抗抑郁样活性;越鞠丸全方醇提物、苍术和川芎可显著缩短小鼠悬尾不动时间和游泳不动时间。结论:越鞠丸全方及香附、苍术、川芎、栀子醇提物均有不同程度的抗抑郁活性,其抗抑郁活性部位/成分可能主要存在于苍术、川芎2味药材之中。     

青蒿琥酯对小鼠实验性肝损伤的保护作用

研究抗疟新药青蒿琥酯(Art)对扑热息痛(AAP)和CCl_4引起的小鼠急性肝损伤的保护作用。实验结果证实,预先给小鼠ip Art200mg/kg,或100mg/kg共3次,其血清GPT和肝脏病变均明显低于对照组;并能降低AAP中毒小鼠的死亡率,对抗AAP所致小鼠早期肝糖元下降。此外,Art尚能显著缩短小鼠戊巴比妥钠睡眠时间,提示它可能具有诱导肝脏药物代谢酶作用。     

消郁安神汤抗肾阴虚型抑郁的初步研究

目的初步探讨自拟消郁安神汤的抗抑郁作用。方法采用小鼠悬尾实验及强迫游泳实验观察消郁安神汤的抗抑郁作用。结果在小鼠强迫游泳实验和小鼠悬尾实验中,消郁安神汤能明显缩短两种"行为绝望"模型小鼠的不动时间,高剂量抗抑郁的效果最明显。结论消郁安神汤对"行为绝望"动物模型有抗抑郁作用。     

花椒多酚类化合物急性给药的抗抑郁作用及机制研究

目的探讨花椒多酚类化合物总提取物（ZPPC）急性给药对ICR小鼠抑郁模型的拮抗作用及可能的机制。方法采用经典的行为绝望抑郁模型,即小鼠悬尾实验和强迫游泳实验,观察ZPPC急性给药对应激小鼠绝望不动时间的影响;同时观察ZPPC对小鼠自主活动的影响,采用荧光分光光度法测定ZPPC对小鼠脑内单胺氧化酶活性的影响。结果与空白组比较,ZPPC（50,100,200mg·kg-1,i.g.）明显缩短小鼠悬尾和强迫游泳实验中的不动时间,其作用类似于阳性对照药丙咪嗪（10mg·kg-1,i.p.）;ZPPC还明显抑制脑内单胺氧化酶的活性。结论 ZPPC急性给药在小鼠行为绝望模型中显示出明显的抗抑郁作用,其作用机制可能与抑制脑内单胺氧化酶活性有关。     

左旋金黄紫堇碱抗精神分裂症作用研究

目的研究左旋金黄紫堇碱(l-SLR)的抗精神分裂症作用。方法采用NMDA受体拮抗剂MK-801在动物模型上诱发精神分裂症的阳性症状、阴性症状及认知损伤;评价了化合物l-SLR对MK-801诱发的精神分裂症的作用;并评价了l-SLR对小鼠锥体外系功能的影响。结果 MK-801(0.3 mg·kg-1,ip)引起大鼠前脉冲抑制损伤,l-SLR(10、15mg·kg-1,ip)能抑制MK-801引起的大鼠前脉冲抑制损伤;l-SLR(30 mg·kg-1,ip)能抑制多巴胺受体激动剂阿扑吗啡(2 mg·kg-1,sc)引起小鼠的攀爬行为,说明l-LSR对MK-801及阿扑吗啡诱发的精神分裂症阳性症状有抑制作用。lSLR(30 mg·kg-1,ip)能抑制MK-801(0.2 mg·kg-1,ip)引起的小鼠群居接触抑制及MK-801诱发的小鼠认知损伤,说明l-SLR能改善MK-801诱发的精神分裂症阴性症状和认知障碍。经典抗精神分裂药氟哌啶醇在治疗剂量下(0.8 mg·kg-1,ip)诱发小鼠木僵行为,l-SLR在抗精神分裂的剂量下(30 mg·kg-1,ip)不会诱发木僵行为。结论化合物lSLR对精神分裂症的阳性症状、阴性症状以及认知障碍均有效,而且其在有效剂量时对锥体外系的影响明显小于氟哌啶醇和l-SPD。     

幼年注射氟西汀诱导的成年昆明种小鼠抑郁模型和胍丁胺抗抑郁活性

幼年雄性昆明种小鼠 (出生后第4天到第21天) 连续给予氟西汀 (10 mg·kg⁻¹, ip, qd), 给药结束后将其正常饲养至成年 (出生后约10周)。研究其行为学改变, 以及慢性给予胍丁胺抗抑郁效应及其对海马腺苷酸环化酶 (AC) 活性的影响。研究发现, 幼年注射氟西汀的小鼠成年后在开场实验中活动显著减少, 而在新奇抑制摄食实验中进食潜伏期明显延长, 在小鼠悬尾实验中显著延长小鼠不动时间, 表现出“抑郁样”行为改变。胍丁胺连续给药 (10 mg·kg⁻¹, ig, bid) 3周后显著增加幼年注射氟西汀成年小鼠的开场活动次数, 并缩短其摄食潜伏期。单次给予胍丁胺 (40 mg·kg⁻¹, ig) 在小鼠悬尾实验中能显著缩短模型小鼠的累计不动时间, 而在放射免疫实验中显著增强海马AC活性。上述结果表明, 幼年小鼠长期给予氟西汀能致小鼠成年后“抑郁样”行为改变, 胍丁胺在该模型动物上则表现出抗抑郁活性, 并且可能与增强海马AC活性有关。     

远志醇提物对抑郁症模型小鼠的保护作用研究

目的:研究远志醇提物对抑郁症模型小鼠的保护作用。方法:通过小鼠悬尾实验、强迫游泳实验、慢性不可预知性应激+开场实验分析远志醇提物的抗抑郁作用。各小实验中雄性小鼠均分为模型对照(等容生理盐水)、氯米帕明(20mg·kg-1)和远志醇提物高、中、低剂量(10、5、2.5g·kg-1)组。结果:高、中、低剂量远志醇提物均可缩短抑郁症模型小鼠悬尾不动时间、游泳不动时间和增加移动格数。结论:远志醇提物对模型小鼠抑郁症状态有一定的改善作用。     

槲皮素-3-芹菜糖基芦丁糖甙对小鼠的抗抑郁作用

给小鼠 ip槲皮素 - 3-芹菜糖基芦丁糖甙( CTN- 986) 0 .31 ,1 .2 5,5mg· kg-130 min后 ,小鼠强迫游泳不动时间显著缩短 ;CTN- 9864- 40μmol·L-1与皮质酮 0 .2 mmol·L-1共孵 PC1 2细胞 48h,可防止皮质酮所致的 PC1 2神经细胞损伤 .结果提示 CTN- 986在小鼠强迫游泳模型上有抗抑郁作用 ,其机理可能与神经细胞的保护作用有关 .     

硫酸锌对实验性心律失常的影响

用6种实验性心律失常动物模型,观察ZnSO_4的抗心律失常作用。ZnSO_4 iv10mg/kg能明显对抗乌头碱和BaCl_2诱发大鼠心律失常,显著缩短CHCl_3-肾上腺素引起家兔心律失常的持续时间.ZnS0_4ip20μg/10g可降低CHCl_3引起小鼠室颤率。但ZnSO_4不能降低CaCl_2引起大鼠室颤率,减少哇巴因引起室性早搏和心室颤动的阈剂量和致死量。     

几种超短肽的抗抑郁作用

超短肽(overshort peptides,简称OSP)是一类由2～4个氨基酸组成的活性肽,存在于体内,参与多方面的生理、生化或病理过程,其中有些OSP分布于CNS,可能参与情感等高级神经活动的调节。为了探讨OSP可能的药用前景,我们对其中5个OSP进行了抗抑郁作用研究。     

遍地金不同提取物的抗抑郁作用

目的筛选遍地金提取物的抗抑郁活性组分,并初步了解各活性组分的抗抑郁作用机制。方法将遍地金提取物分为3个不同的组分,应用6种抗抑郁药理模型筛选抗抑郁活性组分。结果提取物中所有组分的中、小剂量均可显著增加大鼠成功逃避次数,大剂量均可显著减少小鼠的游泳不动时间;水、正丁醇提取组分各个剂量均可显著减少小鼠的悬尾不动时间。但5-HTP致小鼠甩头行为实验中,各组分无显著性差异;利血平及阿朴吗啡引起的体温降低试验中,各组分也无显著性差异。结论遍地金的水、正丁醇提取组分均有较好的抗抑郁作用,水提取组分的效果最佳,正丁醇提取组分次之。     

百合地黄汤抗抑郁活性部位的筛选

 目的：筛选百合地黄汤抗抑郁活性部位。方法：选用小鼠行为绝望模型评价百合地黄汤醇提取物及其4个不同极性部位的抗抑郁作用。结果：百合地黄汤醇提取物及其4个不同极性部位均不同程度地缩短绝望模型中小鼠悬尾和强迫游泳的不动时间,其中以百合地黄汤醇提取物(P<0.01)和正丁醇部位(P<0.001)最为显著。结论：百合地黄汤具有抗抑郁作用,活性成分主要分布在正丁醇部位。     

积雪草总三萜酸及其主要成分的抗抑郁活性研究

目的:探讨积雪草总三萜酸和其主要成分积雪草酸、羟基积雪草酸的抗抑郁作用.方法:采用小鼠强迫游泳实验、小鼠悬尾实验、开野实验和拮抗利血平所致的小鼠眼睑下垂实验,分别以小鼠不动时间、自主活动数和拮抗率作为评价指标.结果:在强迫游泳实验中积雪草总三萜酸、积雪草酸、羟基积雪草酸60 mg/kg、120 mg/kg剂量均能显著缩短小鼠不动时间,在悬尾实验中30 mg/kg、60 mg/kg、120 mg/kg剂量均能显著缩短小鼠不动时间,开野实验结果表明给药后小鼠的自主活动无明显变化,在利血平拮抗实验中积雪草总三萜酸、积雪草酸、羟基积雪草酸均可减少小鼠眼睑下垂.结论:积雪草总三萜酸、积雪草酸、羟基积雪草酸有抗抑郁作用.     

槟榔壳总酚类提取物抗抑郁作用研究

目的:探讨槟榔壳总酚类提取物对抑郁模型小鼠的抗抑郁作用。方法:采用小鼠悬尾、强迫游泳等抑郁模型,以小鼠行为绝望的不动时间作为指标,考察槟榔壳总酚类抗抑郁活性。结果:槟榔壳总酚类320,160 mg.kg-1剂量组均能显著减少小鼠悬尾和强迫游泳的不动时间。结论:槟榔壳总酚类可以改善小鼠的绝望行为,具有明显的抗抑郁作用。     

Individual differences in response to imipramine in the mouse tail suspension test

 The tail suspension test is a behavioural primary screen for detecting potential antidepressant drugs. In this test, a reduction of duration of immobility after treatment with imipramine is obtained in mice of the NMRI strain but not of the CD1 strain. The present experiments evidence important differences between individuals of the latter strain in both the amount of immobility observed in naive mice and the effects of three antidepressants. The reproducibility of the tail suspension-induced behavioural despair was high in individual CD1 male mice and allowed a preselection of spontaneous high and low immobility scorers. Only the high immobility scorers were responsive to imipramine (30 mg/kg), desipramine (30 mg/kg) and paroxetine (10 mg/kg). The percentage of spontaneous high immobility scorers was higher in NMRI (50%) than in CD1 (20%) mice, justifying the use of the former strain for screening potential antidepressants. However, controlling for individual differences in the spontaneous performance in this animal model of depression may provide a useful tool to study behavioural, neurochemical and neuroendocrine correlates of antidepressant action. Received: 24 February 1997 / Final version: 25 June 1997     

Effects of fixed-interval duration on the development of tolerance to decreased responding byl-nantradol

The effects of several types of antidepressants in a recently developed behavioural despair model, the tail-suspension test, are described. Drug effects on the automatically recorded duration of immobility and power of movements were measured in three strains of mice. Only in one strain (NMRI) did almost all antidepressants tested showed the expected reduction in duration of immobility. Tranquillizing drugs, but not stimulants, could be distinguished from antidepressants. The power of movements could not definitively be related to the pharmacological profile of the drugs tested. The use of the tail-suspension test as a rapid and highly predictive behavioural primary screen for antidepressant drugs is suggested.     

Animal models of depression in dopamine, serotonin, and norepinephrine transporter knockout mice: prominent effects of dopamine transporter deletions

Antidepressant drugs produce therapeutic actions and many of their side effects via blockade of the plasma membrane transporters for serotonin (SERT/SLC6A2), norepinephrine (NET/SLC6A1), and dopamine (DAT/SLC6A3). Many antidepressants block several of these transporters; some are more selective. Mouse gene knockouts of these transporters provide interesting models for possible effects of chronic antidepressant treatments. To examine the role of monoamine transporters in models of depression DAT, NET, and SERT knockout (KO) mice and wild-type littermates were studied in the forced swim test (FST), the tail suspension test, and for sucrose consumption. To dissociate general activity from potential antidepressant effects three types of behavior were assessed in the FST: immobility, climbing, and swimming. In confirmation of earlier reports, both DAT KO and NET KO mice exhibited less immobility than wild-type littermates whereas SERT KO mice did not. Effects of DAT deletion were not simply because of hyperactivity, as decreased immobility was observed in DAT+/- mice that were not hyperactive as well as in DAT-/- mice that displayed profound hyperactivity. Climbing was increased, whereas swimming was almost eliminated in DAT-/- mice, and a modest but similar effect was seen in NET KO mice, which showed a modest decrease in locomotor activity. Combined increases in climbing and decreases in immobility are characteristic of FST results in antidepressant animal models, whereas selective effects on swimming are associated with the effects of stimulant drugs. Therefore, an effect on climbing is thought to more specifically reflect antidepressant effects, as has been observed in several other proposed animal models of reduced depressive phenotypes. A similar profile was observed in the tail suspension test, where DAT, NET, and SERT knockouts were all found to reduce immobility, but much greater effects were observed in DAT KO mice. However, to further determine whether these effects of DAT KO in animal models of depression may be because of the confounding effects of hyperactivity, mice were also assessed in a sucrose consumption test. Sucrose consumption was increased in DAT KO mice consistent with reduced anhedonia, and inconsistent with competitive hyperactivity; no increases were observed in SERT KO or NET KO mice. In summary, the effects of DAT KO in animal models of depression are larger than those produced by NET or SERT KO, and unlikely to be simply the result of the confounding effects of locomotor hyperactivity; thus, these data support reevaluation of the role that DAT expression could play in depression and the potential antidepressant effects of DAT blockade.     

豆腐果苷衍生物W0620实验性抗抑郁作用量效关系研究

目的:观察豆腐果苷衍生物W0620对悬尾小鼠不动时间的影响并初步探讨其剂量与效应关系。方法:应用行为绝望抑郁模型——小鼠悬尾实验研究不同剂量W0620对实验小鼠不动时间的影响,同时应用小鼠自主活动实验观察不同剂量W0620对中枢兴奋作用的影响。结果:5.91、17.73、53.20、159.60 mg/kg 4个剂量组对小鼠自主活动均无影响(P>0.05),17.73、53.20、159.60 mg/kg3个剂量组能明显缩短悬尾实验中小鼠的不动时间(P<0.01)。W0620的对数剂量与抗抑郁药效呈现S型量效关系,药效动力学参数如下:Emax80.79 s、Ebase12.13 s、K9.16mg/kg、H3.38、ED509.16 mg/kg、E5046.46 s、ED8013.81 mg/kg、E8067.05 s、ED9017.56 mg/kg、E9073.92 s。结论:W0620有明显抗抑郁作用,其量效关系符合S型曲线,无明显中枢抑制作用。