BACKGROUND & AIMS: :The changes in the hippocampal theta rhythm during an impairment of reference and working memory of radial maze task induced by scopolamine administration were studied. Intraperitoneal injection of scopolamine at doses of 0.5 and 1.0 mg/kg caused a significant increase in the number of total, reference memory and working memory errors. On the other hand, scopolamine significantly increased the hippocampal theta power (5-12 Hz) at doses (0.5 and 1.0 mg/kg) that caused an impairment of reference and working memory. A significant increase in the peak frequency of the hippocampal theta rhythm was also observed with scopolamine, even at a dose of 0.2 mg/kg. At doses of 0.2, 0.5 and 1.0 mg/kg, scopolamine caused a decrease in the locomotor activity during the radial maze task. From these results, it may be concluded that an increase in amplitude of the hippocampal theta rhythm induced by scopolamine is closely associated with memory/learning function of the eight-arm radial maze.

背景与目标： ：研究了东pol碱给药引起的参考障碍和径向迷宫任务的工作记忆障碍期间海马θ节律的变化。腹腔注射东pol碱的剂量为0.5和1.0 mg / kg导致总记忆，参考记忆和工作记忆错误的数量显着增加。另一方面，东pol碱在剂量为0.5和1.0 mg / kg时会显着增加海马theta功率（5-12 Hz），这会导致参照和工作记忆受损。东碱即使在0.2 mg / kg的剂量下也可观察到海马theta节律的峰值频率显着增加。在剂量为0.2、0.5和1.0 mg / kg的情况下，东amine碱引起the迷宫任务期间运动活动的降低。从这些结果可以得出结论，东碱引起的海马θ节律幅度的增加与八臂radial迷宫的记忆/学习功能密切相关。

BACKGROUND & AIMS: OBJECTIVES:Cognitive deficits are one of the frequent symptoms accompanying epilepsy or its treatment. METHODS:In this study, the effect on cognition of intraperitoneally administered antiepileptic drug, pregabalin (10 mg/kg), was investigated in scopolamine-induced memory-impaired mice in the passive avoidance task and Morris water maze task. The effect of scopolamine and pregabalin on animals' locomotor activity was also studied. RESULTS:In the retention phase of the passive avoidance task, pregabalin reversed memory deficits induced by scopolamine (p < 0.05). During the acquisition phase of the Morris water maze pregabalin-treated memory-impaired mice performed the test with longer escape latencies than the vehicle-treated mice (significant at p < 0.05 on Day 5, and at p < 0.001 on Day 6). There were no differences in this parameter between the scopolamine-treated control group and pregabalin-treated memory-impaired mice, which indicated that pregabalin had no influence on spatial learning in this task. During the probe trial a significant difference (p < 0.05) was observed in terms of the mean number of target crossings between vehicle-treated mice and pregabalin-treated memory-impaired mice but there was no difference between the scopolamine-treated control group and mice treated with pregabalin + scopolamine. Pregabalin did not influence locomotor activity increased by scopolamine. DISCUSSION:In passive avoidance task, pregabalin reversed learning deficits induced by scopolamine. In the Morris water maze, pregabalin did not influence spatial learning deficits induced by scopolamine. These results are relevant for epileptic patients treated with pregabalin and those who use it for other therapeutic indications (anxiety, pain).

背景与目标： 目的：认知功能障碍是伴随癫痫或其治疗的常见症状之一。
方法：在这项研究中，在被动回避任务和莫里斯水迷宫任务中，研究了东碱诱导的记忆力受损小鼠腹腔内施用抗癫痫药物普瑞巴林（10μmg/ kg）对认知的影响。还研究了东pol碱和普瑞巴林对动物运动能力的影响。
结果：在被动回避任务的保留阶段，普瑞巴林逆转了东pol碱引起的记忆障碍（p <0.05）。在莫里斯水迷宫的采集阶段中，用普瑞巴林治疗的记忆力受损小鼠比用载体治疗的小鼠进行逃逸潜伏期更长的测试潜伏期（在第5天的p << 0.05，在第6天的p << 0.001显着）。东碱治疗的对照组和普瑞巴林治疗的记忆受损小鼠之间的此参数没有差异，这表明普瑞巴林在此任务中对空间学习没有影响。在探针试验期间，在媒介物处理的小鼠和普瑞巴林治疗的记忆力受损的小鼠之间的平均目标交叉数方面观察到显着差异（p <0.05），但东pol碱治疗的对照组和小鼠之间没有显着差异用普瑞巴林东pol碱治疗。普瑞巴林不影响东pol碱所增加的运动活性。
讨论：在被动回避任务中，普瑞巴林逆转了东pol碱引起的学习缺陷。在莫里斯水迷宫中，普瑞巴林不影响东pol碱引起的空间学习障碍。这些结果与普瑞巴林治疗的癫痫患者以及将其用于其他治疗适应症（焦虑，疼痛）的患者有关。

BACKGROUND & AIMS: We have previously shown that, after peripheral administration, different cytokines affect cognitive functions in mice. In this study, we evaluated the effects of mouse interleukin-6 (IL-6) on the classical behavioural test of scopolamine-induced amnesia for a passive avoidance response in the mouse. Pretraining i.p. administration of this cytokine (0.125 and 0.5 microgram/mouse) significantly reduced the amnesic action of the muscarinic receptor antagonist. As it is well known that brain amino acids are deeply involved in the modulation of cognitive processes we measured the levels of glutamine, aspartic acid, glutamic acid and GABA in the hippocampus and hypothalamus of mice treated with IL-6. At both doses which affected the cognitive functions, this cytokine had no effect on brain levels of measured amino acids. Neither nociceptive thresholds to a thermal stimulus, nor spontaneous locomotor activity were modified by the acute administration of IL-6 (0.5 microgram/mouse). Our data confirm previous observations indicating that peripheral administration of cytokines affects some, but not other brain functions and suggest the involvement of IL-6 in the central modifications induced by the immune activation.

背景与目标： 我们先前已经证明，在外周给药后，不同的细胞因子会影响小鼠的认知功能。在这项研究中，我们评估了小鼠白细胞介素6（IL-6）对东pol碱诱导的健忘症在小鼠中的被动回避反应的经典行为测试的影响。 i.p.的预训练施用这种细胞因子（0.125和0.5微克/小鼠）显着降低了毒蕈碱受体拮抗剂的记忆删除作用。众所周知，大脑氨基酸与认知过程的调节密切相关，我们测量了用IL-6治疗的小鼠海马和下丘脑中谷氨酰胺，天冬氨酸，谷氨酸和GABA的水平。在影响认知功能的两种剂量下，该细胞因子均对脑中测得的氨基酸水平无影响。急性给予IL-6（0.5微克/小鼠）不会改变对热刺激的伤害性阈值或自发运动能力。我们的数据证实了先前的观察结果，表明外周施用细胞因子会影响某些而非其他脑功能，并提示IL-6参与免疫激活诱导的中枢修饰。

BACKGROUND & AIMS: :The objective of this study was to assess the effects of phosphodiesterase type 2 (PDE2) and type 10 (PDE10) inhibition on memory function in the object recognition task using the scopolamine- and MK-801-induced memory deficit model. The effects of the PDE2 inhibitor BAY 60-7550 and the PDE10 inhibitor PQ-10 on object recognition performance were investigated in the scopolamine (0.1mg/kg, i.p.) or MK-801 (0.125 mg/kg, i.p.) model. BAY 60-7550 was tested at a dose of 0.3-3mg/kg (p.o.) in both models; PQ-10 was tested at doses of 0.1-1mg/kg (p.o.) in the scopolamine model and 0.3-3mg/kg in the MK-801 model. All compounds were injected 30 min before the learning trial. Both BAY 60-7550 (1mg/kg) and PQ-10 (0.3mg/kg) attenuated the scopolamine-induced memory deficit. The MK-801-induced memory deficit was reversed after treatment with each PDE inhibitor at a dose of 1mg/kg or higher. PQ10 was highly brain penetrant, whereas 60-7550 levels in the brain were very low after oral treatment. We concluded that since BAY 60-7550 and PQ10 reversed both scopolamine- and MK-801-induced memory deficits, this supports the notion that dual substrate PDE inhibitors might be suitable candidates for cognition enhancement.

背景与目标： ：本研究的目的是使用东pol碱和MK-801诱导的记忆缺陷模型评估2型磷酸二酯酶（PDE2）和10型（PDE10）抑制对物体识别任务中记忆功能的影响。在东pol碱（0.1mg / kg，i.p.）或MK-801（0.125 mg / kg，i.p.）模型中研究了PDE2抑制剂BAY 60-7550和PDE10抑制剂PQ-10对物体识别性能的影响。在两个模型中，BAY 60-7550的剂量为0.3-3mg / kg（p.o.）。在东pol碱模型中以0.1-1mg / kg（p.o.）的剂量测试PQ-10，在MK-801模型中以0.3-3mg / kg的剂量测试。在学习试验之前30分钟注射所有化合物。 BAY 60-7550（1mg / kg）和PQ-10（0.3mg / kg）均减弱了东pol碱诱导的记忆障碍。用每种PDE抑制剂以1mg / kg或更高的剂量治疗后，MK-801诱导的记忆缺陷得以逆转。 PQ10具有很高的脑渗透性，而口服治疗后脑中60-7550的水平非常低。我们得出的结论是，由于BAY 60-7550和PQ10逆转了东pol碱和MK-801诱导的记忆缺陷，因此支持以下观点：双底物PDE抑制剂可能是增强认知的合适候选者。

BACKGROUND & AIMS: :Drug induced cognitive change is generally investigated using small sample sizes. In terms of null hypothesis significance testing (NHST) this can render a meaningful change non-significant, as a result of insufficient power in the statistical model. NHST leads to 'all or none' thinking, where a non-significant result is interpreted as an absence of change. An effect size calculation indicates the magnitude of change which has occurred post-intervention, and therefore whether a significant result is meaningful. We used a scopolamine challenge to demonstrate the usefulness of effect sizes. The aim of the study was to determine how effect sizes could describe the cognitive changes that occur following administration of subcutaneous scopolamine (s.c. scopolamine). Twenty four healthy young males (M = 32.6, sd = 4.5 years) were administered placebo and 0.2 mg, 0.4 mg & 0.6 mg of s.c. scopolamine using a 4-way crossover design. Memory, learning, psychomotor function, attention and executive function were assessed. Scopolamine significantly impaired performance on all tasks in a dose and time related manner. These results demonstrate the functionality of change scores to draw comparisons between different times and doses. This methodology overcomes the limitations of comparisons between studies using different tasks, doses and time at which cognitive functions are measured.

背景与目标： ：药物引起的认知变化通常使用小样本量进行研究。就无效假设显着性检验（NHST）而言，由于统计模型中的功效不足，这可能导致有意义的变化变得不显着。 NHST导致“全有或全无”的思想，其中不重要的结果被解释为没有变化。效应大小的计算表明干预后发生的变化的幅度，并因此表明显着的结果是否有意义。我们使用东pol碱挑战来证明效果大小的有用性。该研究的目的是确定效应大小如何描述皮下注射东pol碱（s.c.东following碱）后发生的认知变化。二十四名健康的年轻男性（M = 32.6，sd = 4.5岁）被给予安慰剂和0.2 mg，0.4 mg和0.6 mg的皮下注射。东pol碱采用四向交叉设计。评估记忆，学习，精神运动功能，注意力和执行功能。东co碱以剂量和时间相关的方式严重损害了所有任务的表现。这些结果证明了变化评分功能可以在不同时间和剂量之间进行比较。这种方法克服了使用不同任务，剂量和时间测量认知功能的研究之间进行比较的局限性。

BACKGROUND & AIMS: BACKGROUND:Plants of the genus Markhamia have been traditionally used by different tribes in various parts of West African countries, including Cameroun. Markhamia tomentosa (Benth.) K. Schum. (Bignoniaceae) is used as an antimalarial, anti-inflammatory, analgesic, antioxidant and anti-Alzheimer agent. The current study was undertaken in order to investigate its anti-amnesic and antioxidant potential on scopolamine-induced cognitive impairment and to determine its possible mechanism of action. METHODS:Rats were pretreated with the aqueous extract (50 and 200 mg/kg, p.o.), for 10 days, and received a single injection of scopolamine (0.7 mg/kg, i.p.) before training in Y-maze and radial arm-maze tests. The biochemical parameters in the rat hippocampus were also assessed to explore oxidative status. Statistical analyses were performed using two-way ANOVA followed by Tukey's post hoc test. F values for which p < 0.05 were regarded as statistically significant. RESULTS:In the scopolamine-treated rats, the aqueous extract improved memory in behavioral tests and decreased the oxidative stress in the rat hippocampus. Also, the aqueous extract exhibited anti-acetylcholinesterase activity. CONCLUSIONS:These results suggest that the aqueous extract ameliorates scopolamine-induced spatial memory impairment by attenuation of the oxidative stress in the rat hippocampus.

背景与目标： 背景：Markhamia属的植物传统上被西非国家（包括喀麦隆）各个地区的不同部落使用。 Markhamia tomentosa（Benth。）K. Schum。 （紫花菊科）被用作抗疟疾，消炎，镇痛，抗氧化剂和抗早老性痴呆剂。进行当前的研究是为了研究其对东pol碱引起的认知障碍的抗记忆和抗氧化潜力，并确定其可能的作用机理。
方法：用含水提取物（50和200 mg / kg，口服）预处理大鼠10天，并单次注射东pol碱（0.7mg / kg，ip），然后在Y迷宫和radial臂迷宫中训练测试。还评估了大鼠海马中的生化参数以探索氧化状态。使用双向方差分析进行统计分析，然后进行Tukey事后检验。 p <0.05的F值具有统计学意义。
结果：在东pol碱治疗的大鼠中，水提取物改善了行为测试的记忆力，并降低了大鼠海马的氧化应激。另外，水提取物表现出抗乙酰胆碱酯酶活性。
结论：这些结果表明，水提取物通过减弱大鼠海马的氧化应激而改善了东pol碱所致的空间记忆障碍。

BACKGROUND & AIMS: To evaluate the usefulness of pirenzepine for diagnostic double-contrast barium enema study of the large bowel, pirenzepine and scopolamine methyl bromide (SMB) were compared in a single, blind, randomized trial. Sixty consecutive patients were enrolled in the study. Quantitative analysis of bowel distention was done by measuring the maximum diameter of the transverse colon before and after drug administration. Four independent observers blindly evaluated distention and mucosal coating of the large bowel and global quality of the images. No differences were found in the diagnostic performance between the two drugs. However, pirenzepine induced a slight but significantly larger distention of the large bowel (68 +/- 12 vs. 65 +/- 8 mm, p = 0.02). Heart rate and rhythm during the study were recorded by ECG. SMB induced tachycardia in all patients (from 72 +/- 15 to 98 +/- 24 beats/min, p < 0.01), whereas pirenzepine did not (from 76 +/- 13 to 78 +/- 20, p = NS). After SMB, one-patient exhibited faintness, and some patients complained of visual accommodation defects, dryness of the mouth, and dizziness. Pirenzepine had a diagnostic performance similar to SMB in avoiding adverse effects elicited by SMB.

背景与目标： 为了评估哌仑西平在大肠诊断性双对比钡灌肠研究中的有用性，在一项单盲，随机试验中比较了吡仑西平和东pol碱甲基溴（SMB）。连续六十名患者被纳入研究。通过在给药之前和之后测量横结肠的最大直径来进行肠扩张的定量分析。四个独立的观察者盲目评估了大肠的扩张和粘膜涂层以及图像的整体质量。两种药物的诊断性能没有发现差异。然而，哌仑西平引起大肠的轻微但明显更大的扩张（68 /-12对65 /-8 mm，p = 0.02）。通过ECG记录研究期间的心律和心律。 SMB诱发所有患者的心动过速（从72 /-15到98 /-24次/分钟，p <0.01），而哌仑西平则没有（从76 /-13到78 /-20，p = NS）。 SMB后，一名患者出现晕厥，有些患者主诉视觉适应性缺陷，口干和头晕。哌仑西平在避免SMB引起的不良反应方面具有与SMB类似的诊断性能。

BACKGROUND & AIMS: :Scopolamine is used clinically, but it is also used as a recreational drug and as an incapacitating drug, in sexual crimes and robberies. In this paper, the authors report the case of a woman with a diminished consciousness following an unsuspected overdose with scopolamine and review published articles on scopolamine poisoning that included concentrations in biological samples. Scopolamine was identified in the patient's serum and urine samples collected 1 h post-admission to intensive care unit (ICU) at concentrations of 8.4 ng/mL and 62,560 ng/mL (169,539 ng/mg creatinine), respectively. In non-fatal cases, the median [interquartile range] of serum scopolamine levels was 1.9 [2.1] ng/mL. The serum concentration found in our case would explain the abrupt clinical presentation suffered by the patient. Scopolamine in urine could be detected up to 48 h after admission. This report illustrates that broad toxicology screening, including scopolamine, should be considered when patients diminished consciousness is observed after ruling out infection or cerebrovascular disease. This can play an important role in identifying this potentially life-threatening etiology.

背景与目标： ：东pol碱在临床上使用，但在性犯罪和抢劫中也用作娱乐性药物和致残药。在本文中，作者报告了一名妇女，因意外服用东following碱过量而失去了知觉，并审阅了有关东pol碱中毒的文章，其中包括生物样品中的浓度。在入院1小时后收集的患者血清和尿液样品中鉴定出co酚胺，浓度分别为8.4 ng / mL和62,560 ng / mL（169,539 ng / mg肌酐）。在非致死病例中，血清东pol碱水平的中位值[四分位数范围]为1.9 [2.1] ng / mL。在我们的病例中发现的血清浓度可以解释患者遭受的突然临床表现。入院后48小时可检测出尿中的co碱。该报告表明，在排除感染或脑血管疾病后观察到患者意识减退时，应考虑进行广泛的毒理学筛查，包括东pol碱。这在识别这种潜在的威胁生命的病因中可以发挥重要作用。

BACKGROUND & AIMS: OBJECTIVE:Alzheimer's disease (AD) is an acquired neurological disorder of cognitive and behavioral impairments, with a long and progressive route. Currently, efforts are being made to develop potent drugs that target multiple pathological mechanisms that drive the successful treatment of AD in human beings. The development of nano-drug delivery systems has recently emerged as an effective strategy to treat AD. METHODS:In the present study, the protective effect of Phytol and Phytol loaded Poly Lactic-co-Glycolic Acid nanoparticles (Phytol-PLGANPs) were evaluated in Wistar rat scopolamine model of AD. RESULTS AND DISCUSSION:The consumption of Phytol and Phytol-PLGANPs significantly ameliorated the cognitive deficits caused by scopolamine on spatial and short term memory. Phytol and Phytol-PLGANPs significantly enhanced the cholinergic effect by inhibiting both acetylcholinesterase and butyrylcholinesterase (AChE & BuChE), β-secretase 1 (BACE1) activity, attenuating macromolecular damage, reducing reactive oxygen species (ROS) and reactive nitrogen species (RNS) level by activating antioxidative defense system (Superoxide dismutase and catalase) and restoring glutathione metabolizing enzyme systems (Glutathione S-transferase) and also regulating the apoptotic mediated cell death. Moreover, in vivo toxicity study suggests that Phytol and Phytol-PLGANPs did not cause any adverse pathological alteration in rats treated with a higher concentration of Phytol-PLGANPs (200 mg/kg). Pharmacokinetic study revealed that Phytol-PLGANPs enhanced the biodistribution and sustained the release profile of phytol in the brain and plasma. CONCLUSION:Overall, the outcome of the study suggests that Phytol and Phytol-PLGANPs act as a potent candidate with better anti-amnesic effects and multi-faceted neuroprotective potential against scopolamine-induced memory dysfunction in Wistar rats.

背景与目标： 目的：阿尔茨海默氏病（AD）是一种认知和行为障碍的获得性神经系统疾病，其病程长且进展。当前，正在努力开发针对多种病理机制的有效药物，所述多种病理机制驱动人类成功治疗AD。纳米药物递送系统的开发近来已经成为治疗AD的有效策略。
方法：在本研究中，在Wistar大鼠东碱AD模型中评估了Phytol和Phytol负载的聚乳酸-乙醇酸共聚物纳米颗粒（Phytol-PLGANPs）的保护作用。
结果与讨论：服用植物甾醇和植物甾醇-PLGANPs可以显着减轻东pol碱对空间和短期记忆的认知缺陷。 Phytol和Phytol-PLGANPs通过抑制乙酰胆碱酯酶和丁酰胆碱酯酶（AChE＆BuChE），β-分泌酶1（BACE1）活性，减弱大分子破坏，降低活性氧（ROS）和活性氮（RNS）的水平来显着增强胆碱能作用通过激活抗氧化防御系统（超氧化物歧化酶和过氧化氢酶）并恢复谷胱甘肽代谢酶系统（谷胱甘肽S-转移酶），并调节凋亡介导的细胞死亡。此外，体内毒性研究表明，在以较高浓度的Phytol-PLGANPs（200μg/ kg）处理的大鼠中，Phytol和Phytol-PLGANPs不会引起任何不良的病理改变。药代动力学研究表明，Phytol-PLGANPs可以增强植物体内在大脑和血浆中的生物分布并维持其释放特性。
结论：总的来说，研究结果表明，Phytol和Phytol-PLGANPs可以作为强效候选物，具有更好的抗遗忘作用，并且具有多种抗东sco碱诱导的Wistar大鼠记忆功能障碍的神经保护作用。

BACKGROUND & AIMS: :Alzheimer's disease (AD) is the most prevalent cause of dementia in the elderly people. The disease is pathologically characterized by extracellular deposition of beta-amyloid peptide (Aβ), cholinergic neurodegeneration and elevation of acetylcholine esterase (AChE) activity in the affected regions. In this study, we investigated the effects of obovatol on memory dysfunction, which was caused by scopolamine. Obovatol (0.2, 0.5 and 1 mg/kg for 7 day) attenuated scopolamine (1 mg/kg, i.p.)-induced amnesia in a dose-dependent manner, as revealed by the Morris water maze test and step-through passive avoidance test. Mechanism studies exhibited that obovatol dose-dependently alleviated scopolamine-induced increase in Aβ generation and β-secretase activity in the cortex and hippocampus. Obovatol also attenuated scopolamine-induced rise in AChE activity in the cortex and hippocampus. Obovatol might rescue scopolamine-mediated impaired learning and memory function by attenuating Aβ accumulation and stabilizing cholinergic neurotransmission, which suggests that the natural compound could be a useful agent for the prevention of the development or progression of AD neurodegeneration.

背景与目标： ：阿尔茨海默氏病（AD）是老年人痴呆症最普遍的病因。该疾病的病理特征是β-淀粉样肽（Aβ）的细胞外沉积，胆碱能神经退行性变和受影响区域乙酰胆碱酯酶（AChE）活性的升高。在这项研究中，我们调查了小ova酚对东碱引起的记忆障碍的影响。 Obovatol（0.2、0.5和1 mg / kg，共7天）以剂量依赖的方式减弱了东pol碱（1 mg / kg，i.p.）引起的健忘症，如莫里斯水迷宫测试和逐步被动回避测试所揭示的那样。机制研究表明，奥波托尔剂量依赖性地减轻了东pol碱所致的皮质和海马中Aβ生成和β-分泌酶活性的增加。 Obovatol还减弱了东pol碱诱导的皮质和海马中AChE活性的升高。 Obovatol可能通过减弱Aβ积累和稳定胆碱能神经传递来拯救东pol碱介导的学习和记忆功能受损，这表明该天然化合物可能是预防AD神经变性发展或进程的有用药物。

BACKGROUND & AIMS: :In order to assess the effects of glucose on drug-induced spatial learning deficits, three experiments were conducted using the Morris water maze. Scopolamine and glucose were injected ip at various stages of training. Rats of Wistar strain served as subjects. In Experiment 1, scopolamine (0.4 mg/kg) and 10, 100, or 500 mg/kg of glucose were administered every day from the start of training, and the effect on acquisition was evaluated. In Experiment 2, scopolamine and 100 or 500 mg/kg of glucose were administered after 6 days of training, and the effect on performance was assessed. In Experiment 3, scopolamine and 500 mg/kg of glucose were injected after 2 days of training, and the effect on the following trial was tested. In all experiments, scopolamine impaired acquisition/performance of the task. Glucose at 500 mg/kg showed a significant enhancing effect on acquisition regardless of scopolamine injection only when injected daily from the start of training (Experiment 1). Glucose injected after the performance has reached asymptote (Experiment 2) did not affect performance, and glucose in the middle of training showed a slight but insignificant enhancing effect (Experiment 3). These results may suggest that the effect of glucose changes as a function of the degree of learning of the spatial learning task. The possibility of task specificity of the glucose effect was also discussed in relation to the cholinergic systems and local cerebral glucose utilization.

背景与目标： ：为了评估葡萄糖对药物引起的空间学习障碍的影响，使用莫里斯水迷宫进行了三个实验。在训练的各个阶段腹腔注射东碱和葡萄糖。 Wistar菌株的大鼠作为受试者。在实验1中，从训练开始每天给予东pol碱（0.4mg / kg）和10、100或500mg / kg的葡萄糖，并且评价对摄取的影响。在实验2中，训练6天后服用东pol碱和100或500 mg / kg葡萄糖，并评估了对运动成绩的影响。在实验3中，训练2天后注射东pol碱和500mg / kg的葡萄糖，并测试了对随后的试验的效果。在所有实验中，东pol碱都会损害任务的获得/执行。仅从训练开始每天注射一次，无论东碱注射量如何，500 mg / kg的葡萄糖均显示出对获取的显着增强作用（实验1）。运动达到渐近线后注射的葡萄糖（实验2）不影响运动，并且在训练过程中葡萄糖显示出轻微但微不足道的增强作用（实验3）。这些结果可能表明，葡萄糖的作用随空间学习任务的学习程度而变化。还讨论了与胆碱能系统和局部脑葡萄糖利用有关的葡萄糖作用的任务特异性的可能性。

BACKGROUND & AIMS: :Transdermal scopolamine, a patch system that delivers 1.5 mg of scopolamine gradually over 72 hours following an initial bolus, was approved in the United States in 2001 for the prevention of postoperative nausea and vomiting (PONV) in adults. Scopolamine (hyoscine) is a selective competitive anatagonist of muscarinic cholinergic receptors. Low serum concentrations of scopolamine produce an antiemetic effect. Transdermal scopolamine is effective in preventing PONV versus placebo [relative risk (RR)=0.77, 95% confidence interval (CI), 0.61-0.98, P = 0.03] and a significantly reduced risk for postoperative nausea (RR=0.59, 95% CI, 0.48-0.73, P < 0.001), postoperative vomiting (RR=0.68, 95% CI, 0.61-0.76, P < 0.001), and PONV (RR 0.73, 95% CI, 0.60-0.88, P = 001) in the first 24 hours after the start of anesthesia.

背景与目标： ：透皮东pol碱是一种贴剂系统，可在初次推注后72小时内逐渐释放1.5 mg东pol碱，已于2001年在美国获准用于预防成人术后恶心和呕吐（PONV）。 Scopolamine（hyscine）是毒蕈碱胆碱能受体的选择性竞争性拮抗剂。东serum碱的低血清浓度会产生止吐作用。相对于安慰剂，经皮东pol碱可有效预防PONV [相对风险（RR）= 0.77，95％置信区间（CI），0.61-0.98，P = 0.03]，并显着降低术后恶心的风险（RR = 0.59，95％CI ，0.48-0.73，P <0.001），术后呕吐（RR = 0.68，95％CI，0.61-0.76，P <0.001）和PONV（RR 0.73，95％CI，0.60-0.88，P = 001）。麻醉开始后的第24小时。

BACKGROUND & AIMS: :The potential involvement of the muscarinic cholinergic system in the underlying mechanisms of prepulse inhibition of the acoustic startle reflex was evaluated in male Sprague-Dawley rats under conditions of varying dose, prepulse intensity, and interstimulus interval. The effects of scopolamine on prepulse inhibition were also directly compared with the effects observed using apomorphine and phencyclidine under the same test parameters. Scopolamine (0. 03-1.0 mg/kg) produced a significant dose-dependent decrease in prepulse inhibition, but had no effect on startle amplitude over the dose range tested. Apomorphine (0.03-1.0 mg/kg) and phencyclidine (0. 1-5.6 mg/kg) produced significant dose-dependent decreases in prepulse inhibition and changes in startle amplitude. The scopolamine-induced decrease in prepulse inhibition varied with prepulse intensity in that the changes produced by scopolamine became smaller in magnitude as the prepulse intensity was increased from 9 to 30 dB above background. On the other hand, apomorphine and phencyclidine decreased prepulse inhibition to approximately the same magnitude across all prepulse intensities tested. The observed decreases in prepulse inhibition produced by scopolamine, apomorphine, and phencyclidine were also dependent on interstimulus interval duration. Scopolamine produced marked decreases in prepulse inhibition at the 100- and 300-ms interstimulus interval durations, but had little or no effect on prepulse inhibition at the 30- and 1000-ms interstimulus interval durations. In contrast, apomorphine decreased prepulse inhibition across all interstimulus interval durations while phencyclidine decreased prepulse inhibition across the 30- to 300-ms interstimulus interval durations. The present findings support the hypothesis that the muscarinic cholinergic system, like the dopaminergic and glutamatergic systems, is directly involved in the mechanisms of prepulse inhibition. However, these three neurotransmitter systems appear to modulate different aspects of prepulse inhibition.

背景与目标： ：在不同剂量，前脉冲强度和刺激间隔的条件下，对雄性Sprague-Dawley大鼠评估了毒蕈碱胆碱能系统潜在地参与声惊跳反射的预脉冲抑制的潜在机制。还可以将东parameters碱对脉冲前抑制的作用与在相同测试参数下使用阿扑吗啡和苯环利定所观察到的作用直接进行比较。东co碱（0. 03-1.0 mg / kg）在前脉冲抑制中产生明显的剂量依赖性降低，但在所测试的剂量范围内对惊吓幅度没有影响。阿扑吗啡（0.03-1.0 mg / kg）和苯环利定（0. 1-5.6 mg / kg）在前脉冲抑制和惊吓振幅变化中产生显着的剂量依赖性降低。东碱引起的前脉冲抑制的降低随前脉冲强度的变化而变化，因为东as碱所产生的变化幅度随前脉冲强度从背景值的9 dB增加到30 dB而变小。另一方面，在所有测试的前脉冲强度中，阿扑吗啡和苯环利定将前脉冲抑制作用降低至大致相同的大小。观察到的东po碱，阿扑吗啡和苯环利定产生的前冲抑制作用的减少还取决于刺激间隔时间。东co碱在100和300毫秒的刺激间隔时间产生的前脉冲抑制作用显着降低，但在30和1000毫秒的刺激间隔时间对前脉冲抑制作用很小或没有影响。相反，阿扑吗啡在所有刺激间隔期间降低了脉冲前抑制，而苯环利定在30-300ms刺激间隔期间降低了前脉冲抑制。本发现支持以下假设：毒蕈碱胆碱能系统，如多巴胺能和谷氨酸能系统，直接参与前脉冲抑制的机制。但是，这三个神经递质系统似乎调节前脉冲抑制的不同方面。

BACKGROUND & AIMS: :A repeated acquisition procedure in a 3-panel runway apparatus was used to investigate the effects to S-adenosyl-L-methionine (SAM) on impairment of working memory produced either by cerebral ischemia or by scopolamine in rats. Cerebral ischemia (2-10 min) produced duration-dependent increases in the number of errors (pushes made on the two incorrect panels located at each choice point) and increased latency (time before the rat reached the goal box). The increase in errors induced by a 5 or 10 min period of ischemia decreased gradually in subsequent training sessions, returning to the control levels in 6 days. The increases in both errors and latency induced by 5 min of ischemia were significantly reduced by 100 and 180 mg/kg SAM administered i.p. immediately after blood recirculation and 1 h before a test conducted 24 h after ischemia. SAM at doses up to 180 mg/kg nevertheless failed to reduce the increases in errors and latency if they were induced by 0.56 mg/kg of scopolamine. These results suggest that SAM has a beneficial effect on memory that has been impaired by cerebral ischemia.

背景与目标： ：在三板跑道装置中重复采集程序，用于研究S-腺苷-L-蛋氨酸（SAM）对大鼠脑缺血或东pol碱产生的工作记忆障碍的影响。脑缺血（2-10分钟）会导致持续时间依赖性的错误数量增加（在每个选择点的两个不正确面板上进行挤压），并增加了潜伏期（大鼠到达目标框之前的时间）。在随后的训练中，由5分钟或10分钟的局部缺血引起的错误增加逐渐减少，并在6天内恢复到对照水平。腹膜内注射100和180 mg / kg SAM可以显着降低缺血5分钟引起的错误和潜伏期的增加。血液循环后立即和缺血后24小时进行测试前1小时。然而，如果由0.56 mg / kg的东pol碱引起，SAM的剂量最高为180 mg / kg时，未能减少错误和潜伏期的增加。这些结果表明，SAM对脑缺血已经损害的记忆具有有益的作用。

BACKGROUND & AIMS: :The object location task is a new procedure evaluating spatial memory abilities in the rat. The aim of the present study was to characterize this behavioural paradigm by pharmacologic means. For this purpose, the effects of the muscarinic receptor antagonist scopolamine and the inhibitor of the nitric oxide synthase L-NAME on object location were assessed in the rat. In a first study, object location was impaired when the delay condition of 60-min was utilized. Subsequently, pre-training administration of scopolamine (0.2 mg/kg but not 0.07 mg/kg) induced delay-dependent performance deficits in this test. These impairments seem to be centrally mediated since the peripheral muscarinic receptor antagonist methylscopolamine (0.2 mg/kg) did not affect object location under the same conditions. Finally, pre-training treatment with L-NAME (30 mg/kg but not 10 mg/kg) also induced delay-dependent performance deficits in the object location task. These results indicate that the object location test is sensitive to pharmacological treatment and could be used for assessing the therapeutic potential of promnesic compounds.

背景与目标： ：对象定位任务是一种评估大鼠空间记忆能力的新程序。本研究的目的是通过药理学方法表征这种行为范例。为此目的，在大鼠中评估毒蕈碱受体拮抗剂东pol碱和一氧化氮合酶L-NAME的抑制剂对物体位置的影响。在第一个研究中，当使用60分钟的延迟条件时，对象的位置会受到损害。随后，在该测试中，东pol碱的训练前给药（0.2 mg / kg而不是0.07 mg / kg）引起了延迟依赖的性能缺陷。由于周围毒蕈碱受体拮抗剂甲基东pol碱（0.2 mg / kg）在相同条件下不影响物体位置，因此这些损伤似乎是中央介导的。最后，使用L-NAME（30 mg / kg但不是10 mg / kg）进行预训练治疗也会在对象定位任务中引起延迟依赖的性能缺陷。这些结果表明，对象位置测试对药理学治疗敏感，可用于评估Promnesic化合物的治疗潜力。