东莨菪碱和毒扁豆碱对吗啡训练大鼠空间学习的影响

目的 :研究吗啡训练大鼠的空间学习障碍与胆碱能系统的关系。方法 :ip吗啡和其他药品 ;通过Morris水迷宫任务检测药物对吗啡训练大鼠空间学习的影响。结果 :10mg·kg- 1 的吗啡对大鼠学习空间任务具有显著的抑制作用 ;10mg·kg- 1 吗啡和 3mg·kg- 1 东莨菪碱联合给药 ,对大鼠学习空间任务的损害更加严重 ;0 .1mg·kg- 1 毒扁豆碱能够降低 10mg·kg- 1 吗啡对大鼠空间学习的影响。结论 :吗啡对学习空间任务的影响机制之一是通过降低胆碱能系统的功能水平实现的     

银杏叶提取物对东莨菪碱所大鼠空间工作记忆障碍的影响

目的 探讨银杏叶提取物对东莨菪碱所致大鼠空间工作记忆障碍的影响.方法 大鼠随机分成3组:正常组、东莨菪碱组和银杏叶治疗组.水迷宫试验,东莨菪碱组按0.4mg/kg腹腔注射,以后每天注射等体积生理盐水,连用6d.正常对照组每天注射与东莨菪碱等体积的生理盐水连用6d;银杏叶治疗组按10mg/kg腹腔注射,1次/d,连用6d.1周后进行Morris水迷宫试验,观察3组大鼠平台逃避潜伏期,并与实验后第1天比较.结果 两次逃避潜伏期在正常组呈非常显著性差异(46.4±17.7,13.4±8.2,P<0.01)东莨菪碱组无统计学差异(23.6±14.3,18.1±9.8,P>0.05),银杏叶组呈显著性差异(27.9±14.3,9.0±3.8,P<0.05).结论 M-型胆碱能受体阻滞剂东莨菪碱能损害大鼠空间工作记忆,银杏叶提取物能改善这种损害,说明银杏叶提取物是通过影响胆碱能系统来发挥其促智作用的.     

银杏叶提取物对东莨菪碱所致大鼠空间工作记忆障碍的影响

目的探讨银杏叶提取物对东莨菪碱所致大鼠空间工作记忆障碍的影响。方法大鼠随机分成3组:正常组、东莨菪碱组和银杏叶治疗组。水迷宫试验,东莨菪碱组按0.4mg/kg腹腔注射,以后每天注射等体积生理盐水,连用6d。正常对照组每天注射与东莨菪碱等体积的生理盐水连用6d;银杏叶治疗组按10mg/kg腹腔注射,1次/d,连用6d。1周后进行Morris水迷宫试验,观察3组大鼠平台逃避潜伏期,并与实验后第1天比较。结果两次逃避潜伏期在正常组呈非常显著性差异(46.4±17.7,13.4±8.2,P<0.01)东莨菪碱组无统计学差异(23.6±14.3,18.1±9.8,P>0.05),银杏叶组呈显著性差异(27.9±14.3,9.0±3.8,P<0.05)。结论M-型胆碱能受体阻滞剂东莨菪碱能损害大鼠空间工作记忆,银杏叶提取物能改善这种损害,说明银杏叶提取物是通过影响胆碱能系统来发挥其促智作用的。     

东莨菪碱对吗啡依赖大鼠条件位置性偏爱激活的抑制作用

目的:观察东莨菪碱(Scopolamine,Sco)对吗啡(Morphine,Mor)依赖大鼠条件位置性偏爱激活的抑制作用。方法:以剂量递增连续皮下(SC)给吗啡6天建立吗啡诱导大鼠条件位置性偏爱(CPP)模型,第7天用生理盐水替代吗啡训练大鼠10天,使形成的CPP逐渐消退,单次SC4mg/kg吗啡激发消退的CPP。部分大鼠在注射吗啡前30分钟分别腹腔注射(ip)Sco(1mg/kg、2mg/kg、3mg/kg)。观察东莨菪碱对吗啡依赖大鼠在伴药箱停留时间的变化。结果:与Mor依赖组相比在SC4mg/kgMor引燃刺激前30min应用Sco1mg/kg、2mg/kg、3mg/kg均可以使大鼠在伴药箱停留时间缩短(P<0.05)。结论:Sco一定程度上抑制Mor引燃的Mor依赖大鼠的条件位置性偏爱激活。     

应激和环境对吗啡暴露大鼠的电生理和行为学影响的研究

目的:研究平台应激、急性吗啡暴露对4周龄和10周龄♂W istar大鼠海马CA1区突触可塑性及空间记忆的影响以及研究丰富环境对大鼠学习记忆、吗啡诱导的条件性位置偏爱(cond itioned p lace preference,CPP)及海马CA1区突触可塑性的影响。方法:电生理实验(在体和离体)和行为学方法(水迷宫和CPP实验),统计采用方差分析(ANOVA)和t检验。结果与结论:(1)慢性应激和/或急性吗啡暴露分别对4周龄和10周龄这两个年龄段的LTP和LTD具有不同作用,存在明显的年龄差异。(2)急性平台应激损害4周龄和10周龄大鼠的记忆,但年龄差异没有显著性;慢性平台应激对10周龄大鼠记忆起易化作用,对4周龄没有明显的影响。(3)急性吗啡暴露(2 mg.kg-1)对4周龄大鼠的记忆有损害作用,而对10周龄大鼠的记忆没有影响。(4)急性应激加吗啡损害了4周龄大鼠的记忆保持,而对10周龄大鼠的记忆保持无影响;慢性应激加吗啡对4周龄大鼠的记忆保持无影响,对10周龄大鼠的记忆保持有易化作用。(5)丰富环境可以增强大鼠的空间学习和记忆能力,增强了吗啡诱导的CPP可能与学习和记忆能力的提高有关;同时,丰富环境对吗啡依赖所致的突触可塑性的损害有保护作用。丰富环境能逆转早期应激所产生的对学习记忆和突触可塑性的损害。     

TAK—147逆转东莨菪碱诱发的大鼠空间记忆障碍

目的:研究和阐明TAK-147对东莨菪碱诱发的大鼠空间记忆损伤的作用.方法:采用Morris水迷宫的程序研究大鼠的空间记忆,利用开场实验方法测定动物自发活动量.结果:在水迷宫的学习过程中,腹腔内注射东莨菪碱(0.4mg/kg,ip)明显延长大鼠上台的潜伏期,而腹腔内注射TAK-147或donepezil(多奈哌齐)能剂量依赖性地改善东莨菪碱诱发的记忆损伤,两药在0.1-1.0mg/kg的剂量时具有显著性差异.在记忆的再生过程中,腹腔内注射东莨菪碱(1.5mg/kg,ip)引起空间记忆再生过程的障碍分别被TAK-147(0.1,0.3和1.0mg/kg)、多奈哌齐(0.3和1.0mg/kg)以及他克林(3和5mg/kg)显著性改善.TAK-147的作用比多奈哌齐略强却明显强于他克林.此外,在开场实验中,TAK-147和多奈哌齐与生理盐水和东莨菪碱相比,对大鼠运动量未产生明显改变.结论:TAK-147在空间认知功能上起重要的作用,进一步证明TAK-147能够成为一个治疗阿尔采默病的理想的胆碱酯酶抑制药.     

组胺对东莨菪碱所致大鼠空间记忆障碍的改善作用(英文)

目的:研究和阐明中枢组胺对东莨菪碱所致大鼠(空间)记忆障碍的作用机制.方法:采用迷宫学习的程序研究大鼠的空间记忆,并利用高效液相法测定脑内组胺含量.结果:侧脑室内注射组胺(100,200 ng)、2-β-噻唑乙胺(200 ng)及4-[4’-(环己氨基硫代甲酰基哌啶)]-4H-咪唑(50μg)或腹腔内注射组胺酸(1000 mg/kg)均可对抗东莨菪碱所致的记忆障碍.相反,4-甲基组胺(50-200 ng)却无明显作用.组胺(200 ng)和组胺酸(1000 mg/kg)均可有效地增加大脑皮层、海马及下丘脑中的组胺含量.结论:中枢组胺可以明显改善东莨菪碱引起的大鼠空间记忆障碍,其作用主要与H_1、H_3受体相关.     

N,N-二甲氨基甲酸5-(1,3,3-三甲基吲哚满)酯与毒扁豆碱促进小鼠视觉暗示空间鉴别学习和记忆的比较

用“Y”迷宫视觉暗示空间鉴别法,观察了TMDMC对小鼠学习获得,记忆保持和再现能力的影响,及其对东莨菪碱损害获得能力的翻转效应,并与毒扁豆碱进行了比较,结果表明,TMDMC能显著促进小鼠学习记忆能力,有效地拮抗东莨菪碱对学习能力的损害,其作用在选择性,安全性,作用强度和持续时间上均优于毒扁豆碱。     

G-CSF对东莨菪碱痴呆模型大鼠认知及ChAT表达的影响

目的观察粒细胞集落刺激因子(G-CSF)对东莨菪碱所致大鼠认知障碍和Ch AT表达的影响。方法24只10月龄Wistar雄性大鼠随机分为三组:空白组(N组)、东莨菪碱组(S组)和G-CSF干预组(G组),分别腹腔注射生理盐水2 ml(N组)、氢溴酸东莨菪碱1 mg/kg(S组)、腹腔注射氢溴酸东莨菪碱1 mg/kg后皮下注射GCSF 50μg/kg,连续5 d。每天给药后3 h进行水迷宫测试其空间学习记忆能力改变,末次水迷宫实验后4%高聚甲醛灌注取脑组织用免疫组化方法观察Ch AT阳性细胞表达。结果行为学变化:各组大鼠第5天潜伏期和游泳距离较第1天短(P<0.05),N组和G组大鼠第5天潜伏期和游泳距离均较S组短(P<0.05)。Ch AT表达变化:N组和G组大鼠海马Ch AT阳性细胞个数均较S组多(P<0.05)。结论 G-CSF可以有效改善东莨菪碱所引起的大鼠认知功能障碍。     

延胡索甲素与左旋延胡索乙素抗吗啡躯体依赖和精神依赖的作用研究

目的 观察并比较延胡索甲素(corydaline,Cor)与左旋延胡索乙素(l-tetrahydropalmatine,l-THP)抗吗啡躯体依赖和精神依赖的作用。方法 SD大鼠随机分为对照组、模型组、Cor组、l-THP组。连续递增sc吗啡9 d后,纳洛酮促瘾,制备吗啡依赖大鼠催促戒断模型,促瘾前30 min ip Cor(40、80 mg/kg)或l-THP(5.0、10.0 mg/kg),观察大鼠戒断症状和体质量的降低;应用旷场实验,观察Cor(5、10 mg/kg)和l-THP(2.5、5.0 mg/kg)对吗啡诱导的大鼠自发活动的影响、对吗啡连续递增给药致大鼠行为敏化效应的影响,以及Cor(10、20、40 mg/kg)和l-THP(2.5、5.0、10.0 mg/kg)对大鼠自发活动的影响。结果 Cor(40、80 mg/kg)、l-THP(5.0 mg/kg)对吗啡催促戒断症状无显著改善作用,10 mg/kg l-THP显著改善大鼠戒断症状(P<0.05);Cor和l-THP对吗啡降低大鼠体质量效应有改善趋势,但差异不显著;Cor 40 mg/kg以下剂量、l-THP 10 mg/kg以下剂量对大鼠自发活动无显著影响;Cor(5、10 mg/kg)和l-THP(2.5、5.0 mg/kg)均可显著降低吗啡诱发的大鼠高活动性行为、行为敏化的形成(P<0.05、0.01)。结论 Cor和l-THP对吗啡所致的大鼠躯体依赖和精神依赖均有不同程度的调节作用,l-THP的起效剂量明显低于Cor。     

PPARγ agonist pioglitazone improves scopolamine-induced memory impairment in mice

Objectives This study was conducted to evaluate the effects of exposure to pioglitazone, a peroxisome proliferator‐activated receptor agonist, on cognitive impairment induced by scopolamine, a muscarinic antagonist, in mice. Methods Pioglitazone (9 mg/kg, 18 mg/kg) was orally administered for 9 days at 30 min before intraperitoneal injection with scopolamine (0.8 mg/kg, i.p.). Cognitive function was evaluated by the passive avoidance test and the Morris water maze test on the 10th day after treatment. Changes in cholinergic system reactivity were also examined by measuring the acetylcholine, acetylcholinesterase and choline acetyltransferase in the hippocampus and cortex. Key findings Scopolamine injection induced impaired performance in the passive avoidance test and the water maze test and severe decrease of cholinergic system reactivity, as indicated by reduced acetylcholine levels, decreased choline acetyltransferase activity and increased acetylcholinesterase activity. Daily administration of pioglitazone significantly increased step‐through latency in passive avoidance test, and significantly decreased the escape latency, and increased the time spent in the platform quadrant in the Morris water maze test. Pioglitazone also protected against scopolamine‐induced cholinergic system deficit, including reduced acetylcholine levels, decreased choline acetyltransferase activity and increased acetylcholinesterase activity in the hippocampus or cortex. Conclusions Pioglitazone demonstrates a significant neuroprotective effect against scopolamine‐induced cholinergic system deficit and cognitive impairment.     

Effect of wild ginseng on scopolamine‐induced acetylcholine depletion in the rat hippocampus

Objectives The ameliorating effects of wild ginseng on learning and memory deficits were investigated in rats. Methods Rats were treated daily with wild ginseng or cultivated ginseng for 7 days at 30 min before scopolamine injection (2 mg/kg, i.p.). After inducing cognitive impairment by the administration of scopolamine, behavioural assessment using the Morris water maze was performed. Changes in cholinergic system reactivity were also examined by measuring the immunoreactive neurons of choline acetyltransferase and the reactivity of acetylcholinesterase in the hippocampus. Key findings Scopolamine injection induced impaired performance in the water maze test and severe cell losses in hippocampal cholinergic neurons, as indicated by decreased choline acetyltransferase immunoreactivity and increased acetylcholinesterase reactivity. Daily administration of wild ginseng produced a significant improvement in the escape latency for finding the platform in the Morris water maze and reduced the loss of cholinergic immunoreactivity in the hippocampus. The reduced expression of brain‐derived neurotrophic factor mRNA due to the scopolamine injection was recovered to normal levels by the administration of wild ginseng. Conclusions Wild ginseng demonstrates a significant neuroprotective effect against scopolamine‐induced neuronal and cognitive impairment.     

石杉碱甲改善老年大鼠水迷宫操作记忆障碍(英文)

目的:测试石杉碱甲对自然衰老及东莨菪碱导致的空间记忆缺损的作用。方法:采用大鼠的水迷宫操作,检测石杉碱甲对获得及记忆的作用。结果:连续7天获得试验期间,皮下注射石杉碱甲0.1-0.2mg/kg能明显缩短老年大鼠找到平台的潜伏期。在第8天撤去平台的记忆测试,石杉碱甲0.1,0.2与0.4 mg/kg明显延长老年大鼠在该平台区的游泳时间。单次腹腔注射东莨菪碱0.1mg/kg明显损害已训练达标老年大鼠的空间记忆。皮下注射石杉碱甲0.4 mg/kg明显翻转东莨菪碱产生的记忆损害作用。结论:石杉碱甲能改善老年大鼠自然衰老或东莨菪碱产生的记忆障碍。     

Reversal of morphine-induced memory impairment in mice by withdrawal in Morris water maze: possible involvement of cholinergic system

The effects of morphine and morphine withdrawal on memory performance were examined in mice by using Morris water maze task. Morphine-induced memory impairment at the doses of 5 and 10 mg/kg recovered after repeated administration. Oxotremorine, a muscarinic receptor agonist, at the dose of 0.1 mg/kg ip, and physostigmine, a cholinesterase inhibitor, at the dose of 0.1 mg/kg ip, significantly antagonized morphine (10 mg/kg sc)-induced memory impairment in mice. Furthermore, repeated naloxone (0.5 mg/kg ip) attenuated scopolamine (0.2 mg/kg ip)-induced memory impairment. By using escalating doses of morphine for 13 days, morphine-induced memory impairment was continuously maintained. When withdrawal was precipitated by naloxone (5 mg/kg ip), or administration of oxotremorine (0.1 and 0.2 mg/kg ip) or physostigmine (0.05 and 0.1 mg/kg ip), the impairment was completely reversed. These results suggest that morphine-induced memory impairment could be partially due to the inhibition of the central cholinergic activity.     

Huperzine A ameliorates the impaired memory of aged rat in the Morris water maze performance

AIM: To determine the memory-improving properties of huperzine A in aged rats with memory impairments naturally occurring or induced by scopolamine. METHODS: Morris water maze was used to investigate the effects of huperzine A on the acquisition and memory impairments. RESULTS: During 7-day acquisition trials, aged rats took longer latency to find the platform. Huperzine A (0.1-0.2 mg/kg, s.c.) could significantly reduce the latency. In the probe trials on the eighth day, huperzine A (0.1, 0.2 and 0.4 mg/kg, s.c.) significantly increased the time in the quadrant where plateform had disappeared in aged rats. In the acute experiment, scopolamine (0.1 mg/kg, i.p.) significantly impaired spatial memory in the trained aged rats. Huperzine A (0.4 mg/kg, s.c.) significantly reversed the memory deficits induced by scopolamine. CONCLUSION: Huperzine A ameliorates the impaired memory naturally occurring or induced by scopolamine in aged rats.     

Assessment of a cholinergic contribution to chlordiazepoxide-induced deficits of place learning in the Morris water maze.

This investigation sought to characterize the interaction between benzodiazepine and cholinergic systems in place learning in the Morris water maze. In the first experiment, rats were treated with scopolamine (1 mg/kg) alone or concomitantly with one of two doses of flumazenil (15 and 30 mg/kg) or with chlordiazepoxide (5 mg/kg) alone or concomitantly with flumazenil (15 mg/kg). Chlordiazepoxide and scopolamine severely impaired place learning but not cue learning. The low dose of flumazenil completely reversed the impairment produced by chlordiazepoxide and both high and low doses of flumazenil attenuated the place learning deficit produced by scopolamine. Neither dose of flumazenil affected place learning when administered alone. In the second experiment, rats were administered chlordiazepoxide (5 mg/kg) or scopolamine (1 mg/kg) alone or concomitantly with one of four doses of physostigmine (0.05, 0.10, 0.25, and 0.5 mg/kg). Once again, both chlordiazepoxide and scopolamine impaired place but not cue learning. Physostigmine reversed the impairment produced by scopolamine in a dose-dependent manner but failed at every dose to attenuate the impairment produced by chlordiazepoxide. The higher doses of physostigmine impaired place learning when administered alone. None of the drug treatments impaired cue learning. Together, these results suggest that the scopolamine-induced impairment of place learning is due to an increase in benzodiazepine/GABA activity, and contradict the notion that benzodiazepines impair memory by cholinergic mechanisms.     

Coadministration of huperzine A and ligustrazine phosphate effectively reverses scopolamine-induced amnesia in rats

In the present study, whether coadministration of huperzine A (HA) and ligustrazine phosphate (LP) could effectively improve the memory deficits in association with ameliorating cholinergic impairment and oxidative stress in the scopolamine-induced amnesia rats was assessed. The effects of treatment with Coa [HA (0.14 mg/kg, i.g.) and LP (110 mg/kg, i.g.)] on amnesia were investigated in Morris water maze. Furthermore, the effects on the activities of acetylcholinesterase (AChE) and antioxidant enzymes within the cerebral cortex and hippocampus were evaluated, and the lipid peroxidation product malondialdehyde (MDA) was also analyzed. As a result, coadministration of HA and LP for 10 consecutive days could markedly reverse the scopolamine-induced learning and memory impairment determined by the Morris water maze test. Moreover, AChE activity was significantly inhibited, and superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px) activities were significantly increased with a remarkable reduction in the level of MDA. In conclusion, coadministration of HA and LP effectively prevented cholinergic impairment and oxidative damage, thereby resulting in improvement of spatial learning memory in rats induced by scopolamine. The results suggested that coadministration of HA and LP might offer a novel poly-therapeutic drug regimen for preventing Alzheimer's disease (AD).     

Cocaine in adolescent rats produces residual memory impairments that are reversible with time

Rats received injections (subcutaneous) of either 10 or 20 mg/kg cocaine on postnatal days 26-33, while lab chow-fed and pair-fed controls received saline. Spatial memory in a Morris water maze was assessed on four different occasions commencing 10 days postcocaine and ending approximately 12 months later. To determine whether there existed long-term changes in cholinergic processes, maze performance was evaluated following 1 mg/kg scopolamine challenge 4 months postcocaine. Subjects survived under standard laboratory housing conditions until they died. Results from the first assessment indicated a working memory deficit in the low-dose cocaine group and a long-term memory impairment in the high-dose cocaine group. These decrements neither were permanent nor were exacerbated by age-related processes in that cocaine-treated subjects performed at control levels on subsequent assessments. An exception to this was the results derived from the third assessment indicating that animals previously treated with 20 mg/kg cocaine were impaired when challenged with scopolamine. Examination of mortality rates revealed that cocaine-treated rats died significantly sooner than lab chow-fed control subjects. Taken together, these data indicate that cocaine during adolescence causes residual, but not permanent, deleterious effects on memory that may be mediated by alterations in cholinergic neurochemistry. More provocatively, the results showed that cocaine during adolescence shortened the lifespan of rats. This latter finding suggests that cocaine during adolescence may produce residual physiological effects that last well into adulthood.     

The effects of daidzin and its aglycon,daidzein, on the scopolamineinduced memory impairment in male mice

In this study, the effect of daidzin or daidzein isolated from Pueraria lobata on the memory impairments induced by scopolamine was assessed in male mice using the passive avoidance and the Morris water maze tasks. Administration of daidzin (5 mg/kg) or daidzein (5 mg/kg) significantly reversed the scopolamine (1 mg/kg)-induced cognitive impairments in male mice as evidenced by the passive avoidance test (p < 0.05) and on the Morris water maze test (p < 0.05). Moreover, the ameliorating effects of daidzin or daidzein were antagonized by tamoxifen (1 mg/kg), the nonspecific estrogen receptor antagonist. These results indicate that daidzin or daidzein may be useful in cognitive impairment induced by cholinergic dysfunction, and this beneficial effect is mediated, in part, via estrogen receptor.