• 【东pol碱的中内侧前额叶皮层注射增加了可卡因的器械反应:一项在大鼠中进行的静脉内自给药研究。】 复制标题 收藏 收藏
    DOI:10.1016/s0361-9230(99)00214-2 复制DOI
    作者列表:Ikemoto S,Goeders NE
    BACKGROUND & AIMS: :The present experiments examined the effects of muscarinic cholinergic receptor blockade in the nucleus accumbens (NAC) and medial prefrontal cortex (MPC) on intravenous cocaine self-administration. Adult male Sprague-Dawley rats were implanted with chronic indwelling jugular catheters and guide cannulae stereotaxically aimed at the NAC or MPC. The rats were then given the opportunity to intravenously self-administer cocaine (0.8 mg/kg/infusion) during daily 2-h sessions. Intra-NAC microinjections of methyl-scopolamine (2, 4, 8, 16, and 32 microg/side) or vehicle did not affect either the number of lever presses made or infusions delivered. On the other hand, intra-MPC injections of scopolamine significantly increased responding, although there was only a trend for an increase in the number of cocaine infusions. The effects of intra-MPC injections of scopolamine (8 and 16 microg/side) on locomotor activity were also evaluated. Intra-MPC injections of scopolamine (16 microg/side) produced significant increases in locomotor activity. However, these same microinjections decreased locomotor activity when the animals also received cocaine (15 mg/kg, i.p.). These results suggest that cholinergic neurotransmission at muscarinic receptors in the MPC is involved in regulating cocaine-maintained responding.
    背景与目标: :本实验研究了伏伏核(NAC)和内侧前额叶皮层(MPC)中毒蕈碱胆碱能受体阻滞对静脉注射可卡因自我给药的影响。将成年雄性Sprague-Dawley大鼠植入慢性留置颈静脉导管,并立体定向引导套管对准NAC或MPC。然后,在每天的2小时疗程中,给大鼠提供了静脉内自行施用可卡因(0.8毫克/千克/输注)的机会。甲基东sco碱(2、4、8、16和32微克/面)或媒介物的NAC内微注射既不影响杠杆按压的次数,也不影响输注量。另一方面,MPC内注射东pol碱的反应显着增强,尽管可卡因输注次数仅有增加的趋势。还评估了东pol碱MPC内注射东pol碱(每侧8和16微克)对运动活性的影响。东pol碱的MPC内注射(16微克/面)可显着提高运动能力。但是,当动物也接受可卡因(15 mg / kg,腹腔注射)时,这些相同的显微注射会降低运动能力。这些结果表明,MPC中毒蕈碱受体的胆碱能神经传递参与调节可卡因维持的应答。
  • 【MK-801诱导和东碱诱导的过度活跃的大鼠,长期用MK-801进行了新生儿治疗。】 复制标题 收藏 收藏
    DOI:10.1097/FBP.0000000000000003 复制DOI
    作者列表:Furuie H,Yamada K,Ichitani Y
    BACKGROUND & AIMS: :This study investigated the effects of chronic neonatal blockade of N-methyl-D-aspartate (NMDA) receptors on NMDA and muscarinic acetylcholine receptor-mediated neurotransmission in adulthood. Rats neonatally treated chronically with MK-801/saline were tested for 40 min, at the age of 14-16 weeks, for locomotor activity in an open field immediately after acute administration of MK-801 (0.2 mg/kg) or scopolamine (0.4-2.0 mg/kg). Rats neonatally treated with MK-801 showed significantly higher locomotor activity than those treated with saline. Acute MK-801 administration caused hyperlocomotion regardless of neonatal treatment, but the effect was more potent in rats neonatally treated with MK-801. In contrast, acute scopolamine administration did not cause hyperlocomotion in rats neonatally treated with saline, but significantly increased locomotion in those neonatally treated with MK-801. The results suggest that chronic neonatal NMDA receptor blockade causes changes in glutamatergic and cholinergic transmission in adulthood long after the cessation of treatment.
    背景与目标: :这项研究调查了成年期慢性新生儿N-甲基-D-天冬氨酸(NMDA)受体对NMDA和毒蕈碱乙酰胆碱受体介导的神经传递的影响。在MK-801(0.2 mg / kg)或东pol碱(0.4 -2.0 mg / kg)。新生儿用MK-801治疗的大鼠显示出比用生理盐水治疗的大鼠明显更高的运动能力。不论新生儿如何治疗,急性给予MK-801都会引起运动过快,但是在用MK-801新生儿治疗的大鼠中,这种作用更为有效。相比之下,东acute碱的急性给药在用盐水新生的大鼠中并未引起运动过度,但是在用MK-801新生的大鼠中运动明显增加。结果表明,慢性新生儿NMDA受体阻滞在停止治疗后很长一段时间内会引起成年后谷氨酸能和胆碱能传递的变化。
  • 【东co碱会损害记忆力,并降低额叶的顶视视觉P3幅度,但不会降低。】 复制标题 收藏 收藏
    DOI:10.1016/s0301-0511(99)00023-x 复制DOI
    作者列表:Potter DD,Pickles CD,Roberts RC,Rugg MD
    BACKGROUND & AIMS: :It has been suggested that the P3 event-related potential (ERP) may mark the operation of certain working or long-term memory processes. It has also been reported that cholinergic blockade by scopolamine induces significant memory impairment and is associated with an increased latency, as well as amplitude reduction or abolition of the auditory P3, thus supporting hypothesised links between P3 and long-term memory function. An intriguing anomaly is that, while visual P3 latency is also increased by scopolamine, amplitude is not changed. The aim of this study was to make a more detailed assessment of the effects of scopolamine on the visual P3 at a drug dose known to induce memory impairment. After drug administration, memory performance was significantly impaired and visual P3 latency was significantly increased. There was little evidence of parietal P3 amplitude reduction, but frontal P3 amplitude was significantly reduced in both target and non-target conditions. These findings, when considered in the light of a more recent study of the effects of scopolamine on auditory P3, suggest that cholinergic blockade produces a common effect in both visual and auditory modalities of significant frontal P3 amplitude reduction, but no significant parietal P3 amplitude reduction. These results are consistent with the view that there are modality-independent generators of the parietal and frontal P3. The finding of drug-induced memory impairment and modulations of frontal ERP deflections is also consistent with recent evidence of a significant role for regions of the frontal lobe in encoding and retrieval of long-term memories.
    背景与目标: :已建议,P3事件相关电位(ERP)可能标志着某些工作或长期记忆过程的运行。还已经报道了东pol碱对胆碱能的阻断引起明显的记忆障碍,并与潜伏期延长,听觉P3的振幅降低或取消有关,从而支持了P3和长期记忆功能之间的假想联系。一个有趣的异常现象是,虽然东碱也增加了视觉上的P3潜伏期,但振幅却没有改变。这项研究的目的是更详细地评估东pol碱在已知诱导记忆力受损的药物剂量下对视觉P3的作用。给药后,记忆力显着受损,视觉P3潜伏期显着增加。几乎没有证据表明顶叶P3振幅降低,但在目标和非目标条件下额叶P3振幅均显着降低。当根据东,碱对听觉P3的影响的最新研究来考虑这些发现时,表明胆碱能阻滞在视觉和听觉方式上均产生显着的额叶P3幅值降低但没有显着的顶叶P3幅值降低的共同作用。 。这些结果与以下观点一致,即顶叶和额叶P3有模态无关的生成器。药物诱导的记忆障碍和额叶ERP偏向调节的发现也与额叶区域在长期记忆的编码和检索中起重要作用的最新证据相一致。
  • 【向伏隔核中注射他克林和东pol碱:立即和延迟的审判后治疗对开放视野记忆的相反作用。】 复制标题 收藏 收藏
    DOI:10.1006/nlme.1999.3915 复制DOI
    作者列表:Schildein S,Huston JP,Schwarting RK
    BACKGROUND & AIMS: :Using the paradigm of habituation learning in the open field, we tested the effects of microinjections of the nonspecific acetylcholine-esterase inhibitor tacrine (0.1, 1.0, 10.0 micrograms), and the muscarinic receptor antagonist scopolamine (0.1, 1.0, 10.0 micrograms) into the core of the nucleus accumbens. When injected immediately after the first exposure to the open field (posttrial), tacrine dose-dependently enhanced habituation of rearing behavior during the test on the following day, indicating a facilitation of memory. In contrast, scopolamine impaired habituation of rearing behavior at the two lower doses, but not at the highest dose. When scopolamine or tacrine (10.0 micrograms) was injected with a delay of 5 h after the learning trial, both drugs impaired habituation of rearing on the following day. The effects on locomotor activity differed from those on rearing behavior. Here, habituation on Day 2 was observed only in those animals which had received posttrial injections of vehicle or 10 micrograms of tacrine on the day before, whereas in animals which had received the two lower doses of tacrine, locomotor activity on Day 2 was not significantly decreased. In animals with posttrial treatment of scopolamine, locomotor activity on Day 2 was even enhanced, especially with the lower doses. No such effects were observed when scopolamine or tacrine (10.0 micrograms each) was injected with a delay of 5 h after the learning trial. These results show that cholinergic manipulations aimed at the nucleus accumbens can have substantial effects in this posttrial memory paradigm, which depend on drug, dose, and time of injection, and the specific kind of behavioral measure analyzed. Among others, the findings are discussed with respect to the role of muscarinic and nicotinergic cholinergic mechanisms in the nucleus accumbens on cognitive functions. They may be relevant, for example, for understanding the psychopathology of Alzheimer's disease, since the nucleus accumbens is one of the sites where cholinergic neurons are lost in this neurodegenerative disease.
    背景与目标: :在野外使用习惯性学习范式,我们测试了将非特异性乙酰胆碱酯酶抑制剂他克林(0.1、1.0、10.0微克)和毒蕈碱受体拮抗剂东pol碱(0.1、1.0、10.0微克)微注射到小鼠体内的效果。伏伏核的核心。当他克林在第一次暴露于开阔视野(试验后)后立即注射时,其剂量依赖性地增强了第二天在测试过程中对养育行为的习惯,表明记忆得到了促进。相反,东pol碱在两个较低的剂量下会损害饲养行为的习惯,而在最高剂量下则不会。学习试验后5小时延迟注射东pol碱或他克林(10.0微克)时,两种药物均会损害第二天的饲养习惯。对运动活动的影响与对养育行为的影响不同。在此,仅在前一天接受了媒介物或10微克他克林注射后注射的那些动物中观察到了第2天的习惯,而在接受了两次较低剂量他克林的动物中,在第2天的运动能力没有显着变化减少了。在用东pol碱进行过事后治疗的动物中,第2天的运动能力甚至得到了增强,尤其是在使用较低剂量的情况下。在学习试验后延迟5小时注射东pol碱或他克林(各10.0微克)时,未观察到此类影响。这些结果表明,针对伏隔核的胆碱能操纵可在这种后记忆模型中产生实质性影响,这取决于药物,剂量和注射时间以及所分析的特定行为措施。除其他外,讨论的结果涉及毒蕈碱和烟碱能胆碱能机制在伏隔核中对认知功能的作用。例如,它们可能与了解阿尔茨海默氏病的心理病理有关,因为伏隔核是该神经退行性疾病中胆碱能神经元丢失的部位之一。
  • 5 Behavioral effect of scopolamine in cats. 复制标题 收藏 收藏

    【东pol碱对猫的行为影响。】 复制标题 收藏 收藏
    DOI:10.3109/00207458808990728 复制DOI
    作者列表:Murillo JR,Mendoza DL,Diaz JL
    BACKGROUND & AIMS: :An ethological study was performed on a colony of cats. Their spontaneous behavior was observed following the chronic administration of scopolamine hydrobromide (0.3 mg/kg/day). Forty-four behavioral units grouped under four categories--resting postures, individual actions, grooming and social interactions--were coded. A general decrease of the frequency of the tested behaviors was observed; this was particularly true of those behaviors in response to individual or social stimulus of an affiliative or agonistic type. The results were consistent with former reports in other species suggesting the changes in attention underlie this lack of response.
    背景与目标: :对猫的一个殖民地进行了一项伦理学研究。长期服用东sco碱氢溴酸盐(0.3 mg / kg /天)后,观察到它们的自发行为。对四十四个行为单位进行了编码,这些行为单位分为四个类别:休息姿势,个人动作,修饰和社交互动。观察到测试行为的频率普遍下降。对于那些从属或激动型个体或社会刺激做出反应的行为尤其如此。结果与其他物种以前的报道一致,表明注意力的改变是这种缺乏反应的基础。
  • 【透皮东pol碱减少唾液流量:四年经验。】 复制标题 收藏 收藏
    DOI:10.1177/019459989010300415 复制DOI
    作者列表:Talmi YP,Finkelstein Y,Zohar Y
    BACKGROUND & AIMS: :Scopoderm transdermal therapeutic system (TTS) is applied to prevent nausea and vomiting associated with motion sickness. Dry mouth is the most common side effect, appearing in up to two thirds of the patients treated. We have used this side effect to the benefit of patients with sialorrhea or with difficulties swallowing normally secreted amounts of saliva. More than 100 patients with tumors of the aerodigestive tract before and after surgery, and patients after parotidectomies, after tracheotomies, with peritonsillar abscesses, tonsillitis and pharyngitis, and neurologic disorders were thus treated. Reduced secretion of saliva was seen in 50% to 100% of the treatment groups. Other side effects were minimal and we recommend the use of scopoderm TTS for reduction of salivary flow.
    背景与目标: :Scopoderm透皮治疗系统(TTS)用于预防与晕车有关的恶心和呕吐。口干是最常见的副作用,多达三分之二的患者出现。我们已经将此副作用用于唾液腹泻或吞咽正常分泌的唾液困难的患者。如此治疗了100例术前和术后的消化道肿瘤患者,以及腮腺切除术后,气管切开术后伴有扁桃体周围脓肿,扁桃体炎和咽炎以及神经系统疾病的患者。在50%至100%的治疗组中,唾液分泌减少。其他副作用极少,我们建议使用of皮TTS减少唾液流量。
  • 【东pol碱对八臂radial骨迷宫任务大鼠海马θ节律的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejphar.2006.03.046 复制DOI
    作者列表:Masuoka T,Fujii Y,Kamei C
    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。
  • 【普瑞巴林对东pol碱诱导的失忆症小鼠模型中基于恐惧的条件回避学习和空间学习的影响。】 复制标题 收藏 收藏
    DOI:10.1080/15376516.2016.1273426 复制DOI
    作者列表:Sałat K,Podkowa A,Malikowska N,Trajer J
    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。
  • 【白介素6影响东pol碱诱导的健忘症,但不影响小鼠的脑氨基酸水平。】 复制标题 收藏 收藏
    DOI:10.1097/00001756-199705060-00041 复制DOI
    作者列表:Bianchi M,Ferrario P,Clavenna A,Panerai AE
    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。

  • 【抑制2型或10型磷酸二酯酶可以逆转东pol碱或MK-801引起的对象记忆缺陷。】 复制标题 收藏 收藏
    DOI:10.1016/j.bbr.2012.08.019 复制DOI
    作者列表:Reneerkens OAH,Rutten K,Bollen E,Hage T,Blokland A,Steinbusch HWM,Prickaerts J
    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。
  • 【在心理药理学研究中使用效应大小来表征认知变化的性质:东pol碱的例子。】 复制标题 收藏 收藏
    DOI:10.1002/hup.942 复制DOI
    作者列表:Fredrickson A,Snyder PJ,Cromer J,Thomas E,Lewis M,Maruff P
    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。
  • 【Markhamia tomentosa(Benth。)K. Schum的水提取物的认知增强和抗氧化活性。东pol碱大鼠模型中的茎皮。】 复制标题 收藏 收藏
    DOI:10.1186/s12993-017-0123-6 复制DOI
    作者列表:Ionita R,Postu PA,Beppe GJ,Mihasan M,Petre BA,Hancianu M,Cioanca O,Hritcu L
    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。
  • 【吡伦西平与东pol碱甲基溴在大肠双对比钡灌肠研究中的应用。】 复制标题 收藏 收藏
    DOI:10.1007/s002619900069 复制DOI
    作者列表:Marraccini P,Braccini G,Marrucci A,Boraschi P,Bertellotti L,Testa R
    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。

  • 【意外服用东co碱过量的妇女意识减退。】 复制标题 收藏 收藏
    DOI:10.1093/jat/bkaa135 复制DOI
    作者列表:Barceló B,Gomila I,de-Castro-Ríos A,Perez-Barcena J,Jimenez C,Lendoiro E,Elorza MÁ
    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。
  • 【负载植物磷脂的PLGA纳米颗粒通过减弱Wistar大鼠胆碱酯酶活性,氧化应激和细胞凋亡来改善东碱所致的认知功能障碍。】 复制标题 收藏 收藏
    DOI:10.1080/1028415X.2020.1764290 复制DOI
    作者列表:Sathya S,Manogari BG,Thamaraiselvi K,Vaidevi S,Ruckmani K,Devi KP
    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。

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