Minaprine improves impairment of working memory induced by scopolamine and cerebral ischemia in rats

Using a repeated acquisition procedure in a three-panel runway apparatus, the effects of minaprine on the impairment of working memory produced by scopolamine, ethylcholine aziridinium ion (AF64A) or cerebral ischemia were investigated in rats. Minaprine (3.2–32 mg/kg IP) as well as idebenone (10–100 mg/kg IP) and physostigmine (0.1–0.32 mg/kg IP) dose-dependently reduced the increase of errors (pushes made on the two incorrect panels located at each choice point) induced by 0.56 mg/kg IP scopolamine. Cerebral ischemia for 5 min caused a significant increase of errors in the runway task. Minaprine at 3.2 and 10 mg/kg administered IP immediately after blood recirculation and again 30 min before the runway test conducted 24 h after ischemia, significantly reduced increases in errors expected to occur after 5 min of ischemia. Physostigmine 0.1 mg/kg similarly attenuated the increase in errors in ischemic rats. However, minaprine at doses up to 32 mg/kg IP failed to reduce the increase of errors induced by AF64A 2.5 nmol injected into the dorsal hippocampus. These findings suggest that minaprine exerts an ameliorating effect on amnesia produced by scopolamine and cerebral ischemia, probably through mediation of its stimulant action on central cholinergic systems.     

孕酮和孕烯醇酮硫酸盐对东莨菪碱引起的小鼠记忆损伤的保护作用

目的 :观察孕酮和孕烯醇酮硫酸盐对东莨菪碱引起的小鼠记忆损伤的保护作用。方法 :用东莨菪碱造成小鼠记忆损伤的模型 ,应用被动避暗试验测定潜伏期以评价记忆成绩。结果 :小鼠给予东莨菪碱 (1mg·kg-1,ip)后 ,其潜伏期显著减少 ,表明造成了明显的记忆损伤。孕酮 (1,10mg·kg-1,sc)和孕烯醇酮硫酸盐 (1mg·kg-1,sc)均可以在被动避暗试验中减轻东莨菪碱引起的记忆损伤。结论 :孕酮和孕烯醇酮硫酸盐可改善记忆损伤。     

百两茶提取物对东莨菪碱诱导小鼠学习记忆障碍的影响

目的研究百两茶提取物对东莨菪碱诱导小鼠学习记忆障碍的影响。方法雄性BALB/C小鼠60只,随机分为6组,分别为空白对照组,东莨菪碱模型组,石杉碱甲片组,百两茶提取物低、中、高(100、200、400 mg·kg-1)剂量组,各组连续给药28 d,于试验前4 d除空白对照组外其余各组小鼠腹腔注射东莨菪碱2 mg·kg-1建立小鼠记忆障碍模型,随后进行跳台试验,记录跳下平台的潜伏期,进行水迷宫测试,记录动物5 min内登台时间。测试毕,处死小鼠,分离大脑皮质和海马,匀浆取上清液测大脑皮质和海马中超氧化物歧化酶(SOD)和乙酰胆碱酯酶(Ach E)的含量。结果百两茶提取物高剂量(400 mg·kg-1)能明显增加小鼠跳台潜伏期(P<0.05),缩短水迷宫小鼠登台时间(P<0.05),升高小鼠大脑皮质和海马组织SOD含量和抑制ACh E的活性。结论百两茶提取物具有明显改善学习记忆作用。     

Nociceptin/orphanin FQ and nocistatin on learning and memory impairment induced by scopolamine in mice.

1. Nociceptin, also known as orphanin FQ, is an endogenous ligand for the orphan opioid receptor-like receptor 1 (ORL1) and involves in various functions in the central nervous system (CNS). On the other hand, nocistatin is recently isolated from the same precursor as nociceptin and blocks nociceptin-induced allodynia and hyperalgesia. 2. Although ORL1 receptors which display a high degree of sequence homology with classical opioid receptors are abundant in the hippocampus, little is known regarding their role in learning and memory. 3. The present study was designed to investigate whether nociceptin/orphanin FQ and nocistatin could modulate impairment of learning and memory induced by scopolamine, a muscarinic cholinergic receptor antagonist, using spontaneous alternation of Y-maze and step-down type passive avoidance tasks in mice. 4. While nocistatin (0.5-5.0 nmol mouse-1, i.c.v.) administered 30 min before spontaneous alternation performance or the training session of the passive avoidance task, had no effect on spontaneous alternation or passive avoidance behaviours, a lower per cent alternation and shorter median step-down latency in the retention test were obtained in nociceptin (1.5 and/or 5.0 nmol mouse-1, i.c.v.)-treated normal mice. 5. Administration of nocistatin (1.5 and/or 5.0 nmol mouse-1, i.c.v.) 30 min before spontaneous alternation performance or the training session of the passive avoidance task, attenuated the scopolamine-induced impairment of spontaneous alternation and passive avoidance behaviours. 6. These results indicated that nocistatin, a new biologically active peptide, ameliorates impairments of spontaneous alternation and passive avoidance induced by scopolamine, and suggested that these peptides play opposite roles in learning and memory.     

人参皂苷Rg1脂质体对东莨菪碱诱导大鼠学习记忆障碍的改善及其作用机制

目的：观察人参皂苷Rg1脂质体（Rg1-L）对东莨菪碱诱导大鼠学习记忆障碍的改善，并探讨其相关机制，方法：制备东莨菪碱诱导大鼠学习记忆障碍模型。采用Y型迷宫评价Rg1-L对模型大鼠学习记忆的影响，并测定大鼠大脑皮质中乙酰胆碱酯酶活性。结果：Rg1-L可以显著改善模型大鼠学习记忆功能。同时抑制大脑皮质中乙酰胆碱酯酶活性。结论：Rg1-L对东莨菪碱诱导大鼠学习记忆障碍模型大鼠的学习记忆功能有显著的改善作用，其机制可能与抑制大脑皮质中乙酰胆碱酯酶活性、提高人参皂苷Rg1生物利用度有关。     

孟鲁司特对东莨菪碱模型小鼠学习记忆及脑内胆碱能神经的影响

目的：研究孟鲁司特（Mon）对东莨菪碱（Scop）致痴呆模型小鼠学习记忆及脑内胆碱能神经的影响。方法：将动物按体重随机分为5组,正常对照组[溶媒（Veh）＋Veh]、阴性对照组（Scop＋Veh）、阳性对照组[Scop＋多奈哌齐（Done）2．0mg／kg]、低剂量孟鲁司特组（Scop＋Mon 1.0mg／kg）、高剂量孟鲁司特组（Scop＋Mon2．0mg／kg）。灌胃给药,除正常对照组腹腔注射生理盐水外,其他各组小鼠给药前30min腹腔注射东莨菪碱（1．0mg·kg^-1·d^-1）,连续给药14d后采用Morris水迷宫和Y迷宫实验测定学习记忆功能,并测定脑海马及皮层乙酰胆碱（ACh）水平及乙酰胆碱酯酶（TChE）的活性。结果：与阴性对照组相比,孟鲁司特（1．0、2．0mg·kg^-1·d^-1）能显著缩短Morris水迷宫隐藏平台训练的潜伏期,增加动物在空间探索实验中对目标象限的搜索时间及原平台所在位置的穿越次数,增加Y迷宫实验中正确反应次数。孟鲁司特还能显著降低小鼠海马及皮层乙酰胆碱酯酶活性,增加乙酰胆碱含量。结论：孟鲁司特通过抑制东莨菪碱所致的痴呆小鼠脑内乙酰胆碱酯酶活性增加乙酰胆碱含量,继而改善小鼠学习记忆损害。     

WEB 1881 FU ameliorates impairment of working memory induced by scopolamine and cerebral ischemia in the three-panel runway task

Using a repeated acquisition procedure in a 3-panel runway apparatus, the effect of WEB 1881 FU on impairment of working memory produced either by scopolamine or by cerebral ischemia was investigated in rats and compared with those of aniracetam and Ca hopantenate. Intraperitoneal injection of scopolamine at 0.56 mg/kg significantly increased the number of errors (pushes made on the two incorrect panels of the three panel-gates located at each choice point). WEB 1881 FU at 10-32 mg/kg, p.o., caused a dose-related reduction in the increase of errors expected in the scopolamine-treated rats. Aniracetam at 10-100 mg/kg, p.o., or Ca hopantenate at 100 and 560 mg/kg, p.o., also significantly diminished the increase in errors induced by 0.56 mg/kg of scopolamine. Cerebral ischemia for 5 min significantly increased errors in the 3-panel runway task. WEB 1881 FU at 32 and 56 mg/kg, administered p.o. immediately after blood flow recirculation and again 1 hr before the runway test, conducted 24 hr after ischemia, significantly reduced the increase in errors expected to occur after 5 min of ischemia. Aniracetam at 32 and 100 mg/kg, p.o., similarly diminished the increase in errors in ischemic rats. These findings suggest that WEB 1881 FU has a beneficial effect on memory that has been impaired by scopolamine or by cerebral ischemia.     

小鼠暂时性脑缺血引起学习记忆障碍模型的制备及人参皂甙的保护作用

人参皂甙是人参的主要有效成分。本文在建立小鼠脑缺血再灌注导致学习记忆障碍模型的基础上，用跳台、避暗两种实验方法观察了人参皂甙对小鼠脑缺血再灌注后学习记忆功能的保护作用。结果显示小鼠脑缺血再灌注可以导致学习记忆障碍，而人参皂甙（１０，１００ｍｇ·ｋｇ－１，ｐｏ）可以对这种记忆障碍起到保护作用。     

Tanshinone congeners improve memory impairments induced by scopolamine on passive avoidance tasks in mice

Tanshinones are a group of diterpenoids found in the roots of Salvia miltiorrhiza Bunge which has been used to treat cardiac disease. In the present study, we investigated the effect of the tanshinone congeners, tanshinone I, tanshinone IIA, cryptotanshinone, and 15, 16-dihydrotanshinone I, on learning and memory impairments induced by scopolamine (1 mg/kg, i.p.), a muscarinic antagonist, using passive avoidance tasks in mice. Tacrine was used as a positive control. Tanshinone I (2 or 4 mg/kg, p.o.), tanshinone IIA (10 or 20 mg/kg, p.o.), cryptotanshinone (10 mg/kg, p.o.), and 15, 16-dihydrotanshinone I (2 or 4 mg/kg, p.o.) significantly reversed scopolamine-induced cognitive impairments (P<0.05). Tanshinone I (2 mg/kg, p.o.) and tanshinone IIA (10 or 20 mg/kg, p.o.) were also reversed diazepam-induced cognitive dysfunctions (P<0.05). In addition, cryptotanshinone and 15, 16-dihydrotanshinone I were found to have an inhibitory effect on acetylcholinesterase in vitro with IC(50) values 82 and 25 microM, respectively. Furthermore, cryptotanshinone inhibited acetylcholinesterase activity for 3 h and 15, 16-dihydrotanshinone I for 6 h in an ex-vivo study. These results suggest that tanshinone congeners may be useful for the treatment of cognitive impairment and that their beneficial effects are mediated, in part, by cholinergic signaling enhancement.     

The seed extract of Cassia obtusifolia ameliorates learning and memory impairments induced by scopolamine or transient cerebral hypoperfusion in mice

In the present study, we assessed the effect of the ethanolic extract of the seeds of Cassia obtusifolia (COE) on the learning and memory impairments induced by scopolamine or transient bilateral common carotid artery occlusion (2VO). In a study of the cholinergic dysfunction induced by scopolamine, single COE (25, 50, or 100 mg/kg, p.o.) administration significantly attenuated scopolamine-induced cognitive impairments as determined by the passive avoidance and Y-maze tasks (P<0.05) and also reduced escape-latency on the Morris water maze task (P<0.05). In the 2VO study, COE (50 mg/kg, p.o.) significantly reversed 2VO-induced cognitive impairments in mice by the passive avoidance and the Y-maze tasks (P<0.05). Moreover, COE (50 mg/kg, p.o.) also reduced escape-latency and prolonged swimming time in the target quadrant during a probe trial of the Morris water maze task (P<0.05). In an in vitro study, COE was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC(50) value: 81.6 microg/ml). Furthermore, COE also inhibited acetylcholinesterase activity in an ex vivo study. These results suggest that COE attenuates memory impairment induced by scopolamine or 2VO and that these effects are mediated by enhancing the cholinergic nervous system via acetylcholinesterase inhibition.     

Effects of scopolamine on locomotor activity and metabolic rate in mice

Reduction of metabolic rate occurs in rodents in response to intoxication with several chemicals, including amphetamine. In the present study, cholinergic mediation of locomotor activity and metabolic rate was investigated by measuring the effects of scopolamine on the frequency of photobeam breaks, the rate of CO2 production, and rectal temperature in unrestrained mice. Increasing doses of scopolamine (0, 0.3, 1.0, 3.0, and 10.0 mg/kg IP) increased locomotor activity over a 72-min observation period. CO2 production (as minute volume exhaled CO2, VECO2), measured simultaneously with locomotor activity, was suppressed equally at all doses of the drug. Rectal temperatures taken 72 min after scopolamine declined slightly in a dose-related manner. These results parallel earlier findings with d-amphetamine and suggest that divergent effects on metabolic rate and locomotor activity may be induced by centrally-acting compounds acting on more than one neurochemical system.     

Gly(14)]-Humanin improved the learning and memory impairment induced by scopolamine in vivo.

Humanin is a very recently discovered 24 amino acid linear polypeptide, which protects against cell death induced by either familial Alzheimer's disease mutant of amyloid precursor protein, presenilin-1 or presenilin-2 in vitro. However, it has remained uncertain whether humanin is a useful drug for the animal model of learning and memory deficit. In this study, we evaluated the effects of [Gly(14)]-humanin, a more potent humanin analogue, on the scopolamine HBr (1 mg kg(-1) s.c.)-induced impairment of spontaneous alternation behaviour in the Y-maze, an index of short-term memory in mice. [Gly(14)]-Humanin (1000 pmol 5 microl(-1) i.c.v.) reversed the impairment without affecting the number of arm entries. These results suggest that (I) [Gly(14)]-humanin is a beneficial drug for the impairment of learning and memory and (II) it modulates the learning and memory function mediated via cholinergic systems in mice.     

大黄酚对铅中毒小鼠学习记忆的改善作用及其机制研究

目的研究大黄酚对铅中毒小鼠学习记忆障碍的改善作用,探讨其可能的作用机制。方法采用连续8 d腹腔注射7 mg.kg-1醋酸铅造成铅中毒小鼠模型,应用避暗实验、水迷宫实验,观察腹腔注射大黄酚(10.0、1.0、0.1 mg.kg-1)14 d对铅中毒模型小鼠记忆障碍的改善作用,大黄酚治疗14 d后测定小鼠血铅、脑铅及脑组织中MDA含量SOD,GSH-Px活力,一氧化氮(NO)含量及一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)的活性。结果连续8 d腹腔注射7 mg.kg-1醋酸铅造成铅中毒小鼠学习记忆障碍,使小鼠脑铅、血铅升高,导致小鼠脑组织内SOD和GSH-Px活性降低,使小鼠脑组织内MDA含量增加,小鼠脑组织内NO含量增加,NOS和iNOS活性升高;连续ip大黄酚14d治疗后,可不同程度改善小鼠铅中毒造成的学习记忆障碍,降低血铅及脑铅水平,大黄酚(0.1 mg.kg-1)可升高铅中毒小鼠脑内SOD和GSH-Px的活性(P<0.01),对MDA含量无影响;大黄酚(10.0、1.0 mg.kg-1)可升高铅中毒小鼠脑内SOD和GSH-Px的活性,降低小鼠脑内MDA含量(P<0.01);大黄酚(0.1 mg.kg-1)可降低小鼠脑内NOS、iNOS的活性(P<0.05),对NO含量无影响;大黄酚10.0,1.0 mg.kg-1治疗组可降低小鼠脑内NO含量和NOS、iNOS的活性(P<0.01)。结论大黄酚通过提高铅中毒小鼠脑组织抗氧化酶活性同时降低NOS、iNOS的活性,抑制脂质过氧化,明显拮抗铅诱导的小鼠学习记忆障碍。     

黄精改善小鼠学习记忆障碍等作用的研究

研究了黄精乙醇提取物 (PSEtOH ext.)对小鼠学习记忆能力的影响、PSEtOH ext .及其总皂苷 (PTS)对东莨菪碱 (SCO)所致小鼠记忆获得障碍的影响以及PSEtOH ext .对小鼠急性脑缺血的影响和对大鼠脑组织丙二醛 (MDA)含量的影响 ,结果发现PSEtOH ext .能促进正常小鼠的学习能力 ,PSEtOH ext .及PTS均能改善东莨菪碱致小鼠学习记忆获得障碍 ,PSEtOH ext .能明显延长双侧颈总动脉结扎致急性脑缺血小鼠的生存时间 ,体外实验 ,PSEtOH ext.2 0mg/mL ,10 0mg/mL可显著抑制大鼠脑组织MDA的生成。     

促智药对樟柳碱所致记忆障碍的改善作用

目的：探讨几种促智药对樟柳碱诱导小鼠记忆障碍模型的影响。方法：动物学习、记忆实验用跳台法和避暗法。结果：几种不同剂量的促智药对樟柳碱所致记忆障碍均有不同程度的改善作用。小鼠跳台和避暗行为潜伏期延长，错误次数减少。结论：康宝和长寿康对樟柳碱所引起的记忆障碍有明显的改善作用，与公认的促智西药尼莫地平、奥拉西坦相似。     

大黄酚通过抗氧化应激改善高血氨小鼠学习记忆功能障碍

<正>氨中毒学说在肝性脑病(hepatic encephalopathy,HE)的发生发展中占重要地位。相关研究已明确氨的中枢神经毒性作用[1],包括学习记忆障碍[2]。研究表明,大黄酚具有改善阿尔茨海默病(Alzheimer’s disease,AD)患者的学习记忆和认知功能、提高抗缺氧化能力等多种药理作用[3]。本研究先建立高血氨小鼠模型,通过给予大黄酚,来探讨大黄酚对氨诱导小鼠学习记忆功能障碍的改善作用,报道如下。1材料与方法1.1材料昆明种、健康♂小鼠,体质量25-30 g,由中国医学科学院实验动物中心提供(许可证编号:SCXK京2004     

Effects of scopolamine on learning and memory in monkeys

The effects of scopolamine were evaluated in monkeys responding under operant procedures designed to evaluate drug effects on learning and memory. In one procedure, responding was maintained by food presentation under a multiple schedule. One component of the multiple schedule was a repeated-acquisition task in which the discriminative stimuli for left- and right-key responses changed each session (learning). In the other component, the discriminative stimuli for responses were the same each session (performance). In both components of the multiple schedule, scopolamine produced dose-related decreases in responding; there was little evidence of differential rate-decreasing effects between components. Percent errors in learning were increased in a dose-related manner, whereas percent errors in performance were generally unaffected except at high doses, which also produced substantial decreases in response rate. These results suggest that acquisition is more sensitive to the disruptive effects of scopolamine than is performance. The second procedure utilized repeated acquisition and delayed performance as a technique to study the effects of scopolamine on memory. In this procedure, each session was divided into three phases: acquisition, delay and performance. After a 24-h delay, scopolamine had little or no effect on retention, accuracy or rate of responding. In contrast, after a 60-min delay, scopolamine decreased retention in a dose-related manner. These data suggest that scopolamine produces a greater disruptive effect on short (60-min) versus long (24-h) delays.     

Attenuation of scopolamine induced deficits in navigational memory performance in rats by bis(7) tacrine, a novel dimeric AChE inhibitor

目的：研究他克林的双体衍生物双（７）他克林对东莨菪碱引起的大鼠记忆障碍的影响．方法：采用大鼠Ｍｏｒｉｓ水迷宫固定平台的程序研究空间记忆．以他克林为对照药．结果：东莨菪碱（０３ｍｇ·ｋｇ－１,ｉｐ）使大鼠到达平台的潜伏期明显长于生理盐水对照组．双（７）他克林（０３５μｍｏｌ·ｋｇ－１,ｉｇ或ｉｐ）和他克林（８５２μｍｏｌ·ｋｇ－１ｉｇ;４２６μｍｏｌ·ｋｇ－１ｉｐ）均可对抗东莨菪碱导致的空间记忆障碍;在灌胃及腹腔注射途径下,双（７）他克林的效价,分别强于他克林２４及１２倍．结论：双（７）他克林明显改善东莨菪碱导致的空间记忆障碍,其作用强于他克林．     

Effects of nocistatin on nociceptin-induced impairment of learning and memory in mice

We investigated the effects of nociceptin/orphanin FQ and nocistatin on learning and memory function as measured in a step-down type passive avoidance task and spontaneous alternation of Y-maze with mice. Nociceptin (0.5-5.0 nmol/mouse, i.c.v.) 30 min before the training session or Y-maze test, dose dependently shortened the step-down latency and impaired spontaneous alternation, while there was no significant effect of nocistatin (0.5-5.0 nmol/mouse). Interestingly, nocistatin (5.0 nmol) significantly improved the nociceptin (5.0 nmol)-induced impairment of learning and memory without changing motor activity or response to electric shocks. These results suggest that nocistatin, a new biologically active peptide now found to also counteract the impairment of learning and memory induced by nociceptin, plays an important role in the regulation of learning and memory process in the central nervous system.     

Meserine对胆碱酯酶活性及东莨菪碱诱导痴呆小鼠学习记忆的影响

目的：考察新型胆碱酯酶抑制剂Meserine对胆碱酯酶活性及东莨菪碱（Scopolamine）诱导的胆碱能障碍痴呆模型小鼠学习记忆的影响。方法：选取小鼠脑匀浆、血浆、人源重组AChE（rHuAChE）为体外酶源,测定Meserine抑制AChE／BuChE的活性、选择性及酶动力学。通过鼻腔给药后检测脑部AChE活性和ACh浓度评价Meserine对小鼠脑内胆碱能系统的调节。选用避暗及水迷宫实验考察Meserine对痴呆模型小鼠学习记忆功能的影响。结果：Meserine对AChE和BuChE都具有较好的抑制活性,IC50分别为（65．2±3．2）nmol／L和（86．7±4．9）nmol／L,并对rHuAChE呈现非竞争性抑制。经鼻给药Meserine可显著抑制脑内AChE活性、升高ACh水平,且二者变化的时程具有一致性,给药15min后,AChE抑制活性最强（26．9％）,ACh浓度最高（1269．0ng／g）。行为学实验结果显示,经鼻给药Meserine（10μg／kg）能显著改善东莨菪碱诱导的痴呆模型小鼠的工作记忆及空间学习能力,较模型组具有统计学差异（P〈0．OlVS东莨菪碱组）。结论：上述结果提示Meserine为强效非竞争性胆碱酯酶抑制剂,经鼻给药Meserine可通过调节脑内胆碱能系统有效改善东莨菪碱诱导的痴呆模型小鼠的学习记忆功能。