左炔诺孕酮和炔雌醚复合不育剂（EP-1）对雌性东方田鼠生殖的影响

  本文在实验室条件下通过一次性灌胃的方式研究了左炔诺孕酮-炔雌醚复合不育剂（EP-1）对雌性东方田鼠激素、生殖系统、胎仔数、受孕率的影响及药效持续时间,旨在检验其应用于野外东方田鼠不育控制的价值。结果表明,各浓度EP-1灌胃均能显著提高雌性东方田鼠的子宫系数,使子宫形态发生变化,对卵巢组织造成损伤,影响卵泡和黄体的发育,但是对雌二醇含量和子宫长度没有明显影响;60mg/kg EP-1灌胃能显著提高促卵泡刺激素含量和卵巢系数,而10mg/kg、30mg/kg EP-1灌胃对二者没有明显影响。室内繁殖实验表明,各浓度EP-1灌胃均能不同程度延迟初次怀孕时间,并降低试鼠的怀孕率和胎仔数,但抗生育作用具有可逆性且与药物浓度相关,10mg/kg、30mg/kg和60mg/kg剂量组生殖系统恢复时间分别为16 d、38 d和52 d。     

姜黄素对9月龄APPswe／PSldE9双转基因小鼠行为学的影响

目的应用Morris水迷宫,测试AD模型APPswe／PSldE9双转基因小鼠定位航行及空间搜索等学习记忆和记忆保持能力,评价姜黄素对APPswe／PSldE9双转基因小鼠认知功能的影响。方法将3月龄的APPswe／PSldE9双转基因小鼠随机分为模型组、罗格列酮组（10ms／kg·d）、姜黄素高（400Ing／kg·d）、中（200ing／kg·d）、低剂量组（100mg,,kg·d）,每组6只;并以同月龄遗传背景相同的C57／BL6J小鼠作为对照组。每天灌胃给药1次,连续灌胃6个月。应用Morris水迷宫进行行为学检测。结果姜黄素对APPswe／PSldE9双转基因小鼠空间学习记忆能力障碍有改善作用,尤以姜黄素大剂量和中剂量组效果比较明显。结论姜黄素能改善APPswe／PSldE9双转基因小鼠的认知功能。     

炔雌醚对布氏田鼠繁殖的抑制效果

明确炔雌醚对鼠类繁殖抑制最适剂量及持续有效作用时间,对其后续相关理论研究和实践应用具有基础性作用。本研究以0.5 mg/kg、1.0mg/kg、2.0mg/kg、3.0mg/kg、6.0mg/kg浓度炔雌醚分别连续灌胃雄性和雌性布氏田鼠7d 后,与正常异性配对观察90ｄ。按繁殖启动期、繁殖率和繁殖力等最直观的指标综合评价了5个浓度炔雌醚对雌雄布氏田鼠的不育效果。室内条件下,炔雌醚能够延迟雌雄布氏田鼠的生殖启动,但可能由于样本量小,未达统计显著性。90ｄ 内,一定浓度的炔雌醚能够降低雌雄个体的繁殖率和平均每窝产仔数,同样未达统计显著性。一些浓度的药物能够显著降低布氏田鼠的繁殖力,其抑制效果无剂量相关性。推断炔雌醚对雄性布氏田鼠的最适不育作用浓度为2.0mg/kg左右,对雌性的最适不育作用浓度为1.0mg/kg左右。实际综合应用剂量2.0mg/kg左右,能有效降低布氏田鼠产仔总数,其持续时间可达90d。     

吗啡和胆碱能拮抗剂联合给药对小鼠Y迷宫空间记忆提取及活动性的影响(英文）

吗啡和胆碱能系统的相互作用已在多项研究中提到,本实验想查明吗啡是否能和胆碱能拮抗剂、东莨菪碱以及阿托品共同作用对小鼠的Y迷宫空间识别记忆提取产生影响。采用测试前腹腔给药的方法,选用3种剂量的吗啡(5、1.5、0.5mg/kg),两种剂量的东莨菪碱(1、0.1mg/kg),以及两种剂量的阿托品(0.5、0.1mg/kg),剂量由高到低相配对作为联合给药的手段。其结果表明:1)0.5mg/kg低剂量吗啡与0.1mg/kg低剂量的东莨菪碱,或与0.1mg/kg低剂量的阿托品联合给药的小鼠,在记忆提取测试中,空间探查行为(各臂停留时间百分比)对新异臂没有偏好,而新奇探索行为(各臂访问次数百分比)仍保持了对新异臂的偏好,而相应剂量药物单独给药的小鼠记忆提取均没有被损害;2)吗啡能和东莨菪碱相互作用使小鼠的活动性显著增强。暗示吗啡和胆碱能拮抗剂对小鼠空间记忆提取的破坏存在一定程度的相互作用。     

大蒜素对D-半乳糖致衰老小鼠学习记忆调节作用

目的 观察大蒜素对D-半乳糖(D-ga1)致小鼠衰老模型学习记忆的调节作用.方法 小鼠随机分为正常对照组、模型对照组、大蒜素低剂量组(10 mg/kg·d)、中剂量组(20 mg/kg·d)、高剂量组(40 mg/kg·d),连续给药8周后采用Y型迷宫、跳台实验检测小鼠学习记忆能力及体内丙二醛(MDA)和超氧化物歧化酶(SOD)水平. 结果 与正常对照组比较,模型对照组小鼠跳台错误次数和迷宫错误次数明显增多,体内MDA含量升高,SOD活性下降;大蒜素组小鼠跳台错误次数减少,迷宫测试潜伏期缩短,体内MDA含量下降,SOD活性升高,并呈现剂量依赖性.结论 大蒜素能改善衰老小鼠学习记忆能力,其机制可能与抗氧化作用有关.     

左炔诺孕酮和炔雌醚复合物(EP-1)及组分对鼠类不育效果的研究进展

由于当前传统灭杀带来的一系列问题,鼠害不育控制逐渐受到重视。自张知彬等2004年率先报道左炔诺孕酮和炔雌醚复合物(EP-1)对野生鼠类不育效果的研究以来,国内多个研究团队对EP-1及其组分的不育效果、剂量、饵料制作、环境安全性、行为与分子机理等方面开展了大量的验证和完善研究,取得了许多重要的进展。这些结果进一步说明EP-1及组分对鼠类具有很好的不育效果,并具有两性不育、高效低量、可持续、相对环保与安全、野外投放方便、经济可行等特点。EP-1或炔雌醚毒饵的不育剂量约为10-50μg/m L(0.001%-0.005%),甚至更低;其组分在土壤和水体的半衰期约为5-16 d和小于3 d。在鼠类繁殖的早期,采取野外一次饱和投放即可有效降低全年鼠类的繁殖,效果可延续至第二年。可见,EP-1及其组分有望成为鼠害控制的一个新手段。建议今后进一步加强野外不育与跨年持续效应的验证、环境安全性评价和行为生态学机制等研究工作。     

炔雌醚对小鼠空间记忆力及情绪的作用

为检测炔雌醚对雄性昆明小鼠空间记忆力和抑郁水平的作用,我们将18只雄性昆明小鼠分为3组:对照组、10 mg/kg组和20 mg/kg组,通过Y迷宫、强迫游泳和悬尾3组实验,检测炔雌醚对其空间记忆力及抑郁水平的作用。结果发现:(1)两个实验组小鼠的空间记忆力与对照组相比并无显著变化;(2)10 mg/kg实验组小鼠的抑郁水平较对照组有所降低,但是20 mg/kg炔雌醚对小鼠的抑郁水平没有产生显著变化。由此我们得出结论:经过炔雌醚处理的小鼠,空间记忆力没有发生变化,也不会导致小鼠抑郁水平上升,表明炔雌醚不会对小鼠的生存能力造成明显的影响。本研究为进一步明确不育剂对鼠类的作用提供了一定的理论依据。     

初步探讨鸟嘌呤核苷、姜黄素对AD双转基因小鼠学习记忆的影响

目的通过Morris水迷宫检测学习记忆和记忆保持能力,判断鸟嘌呤核苷、姜黄素对4月龄APPswe/PS1dE9双转基因小鼠认知功能的影响。方法将3月龄APPswe/PS1dE9双转基因小鼠随机分为模型组、盐酸多奈哌齐组0.92 mg/(kg·d)、鸟嘌呤核苷组20 mg/(kg·d)、姜黄素组200 mg/(kg·d)、姜黄素200 mg/(kg·d)和鸟嘌呤核苷组20 mg/(kg·d),每组12只;并以同月龄野生型C57/BL6J小鼠作对照。每天给药1次,连续给药1个月。应用Morris水迷宫进行行为学检测。结果鸟嘌呤核苷、姜黄素对空间探索、定位航行障碍有改善作用,尤其以姜黄素组明显。结论鸟嘌呤核苷、姜黄素能改善APPswe/PS1dE9双转基因小鼠的早期出现的认知障碍。     

妊娠期和哺乳期双酚A暴露对幼年子代小鼠焦虑和抑郁行为的影响

双酚A(bisphenol-A,BPA)对脑和行为发育的低剂量效应已引起广泛关注。本研究分别于妊娠最后2周和分娩后前2周母鼠灌胃BPA(0.4和4 mg/kg.d),然后以旷场、高架十字迷宫、明暗箱、镜子迷宫、强迫游泳和被动回避箱等模型,分别测试幼年期(生后21～28 d)子代小鼠的行为,探讨围生期不同阶段的BPA暴露对幼年仔鼠自发活动、探究、焦虑、抑郁和被动回避记忆等行为的影响。结果表明,围生期不同阶段的BPA暴露对这些行为的影响不同,主要表现为:妊娠期BPA暴露促进幼年仔鼠的活动性,减弱其焦虑状态,提高雄性仔鼠的探究能力,促进雌性仔鼠的被动回避记忆;哺乳期BPA暴露减少幼年仔鼠的活动性,但对其焦虑行为的影响相对较弱,不影响仔鼠的探究能力和被动回避记忆;而妊娠期和哺乳期BPA暴露均加剧幼年仔鼠的抑郁行为。以上结果提示,妊娠期和哺乳期BPA暴露均可影响幼年仔鼠的焦虑、抑郁、被动回避记忆等多种行为,而妊娠期可能是BPA影响的更敏感时期。     

基于Morris 水迷宫探讨不同贮食行为鼠类的空间记忆

鼠类的贮食方式(分散或集中)与其空间记忆能力有关,但有关两者的定量关系尚缺少实验证据。朝鲜姬鼠(Apodemus peninsulae)分散或集中贮藏食物;社鼠(Niviventer confucianus)、黑线姬鼠(A. agrarius)、昆明小鼠(Mus musculus)仅集中贮藏食物。利用Morris 水迷宫对4 种鼠的空间记忆能力进行了评估,以探讨其空间记忆能力与食物贮藏方式间的联系。结果发现:在5 d 的定位航行实验中,4 种鼠找到隐藏平台的潜伏期均呈现出显著的下降趋势,其中朝鲜姬鼠潜伏期最短,黑线姬鼠与社鼠次之,昆明小鼠最长。在空间探索实验中,朝鲜姬鼠、黑线姬鼠和社鼠穿越平台的次数显著大于昆明小鼠;实验鼠在目标象限内的时间比和路程比为:朝鲜姬鼠> 黑线姬鼠> 社鼠>昆明小鼠,但差异不显著。结果表明具有分散贮藏行为的朝鲜姬鼠的空间记忆能力较仅具有集中贮藏行为的其它鼠种强,暗示鼠类的食物贮藏方式与其空间记忆能力有一定联系。     

Preventive action of Ginkgo biloba in stress- and corticosterone-induced impairment of spatial memory in rats

In this study, we tested preventive effects of a natural medicine the extract of Ginkgo biloba (EGB 761) on post-stress cognitive dysfunction. Exposure to chronic restraint stress in rats and psychosocial stress in humans has been shown to alter cognitive functions such as learning and memory and have been linked to the pathophysiology of mood and anxiety disorders.Our findings indicate that chronic restraint stress impaired egocentric spatial memory as observed in the eight-arm radial maze but it did not alter the allocentric spatial memory in the Morris water maze. In control rats EGB 761 (100 mg/kg, orally) improved spatial memory in these two tests. Also, EGB 761 normalized cognitive deficits seen in rats chronically stressed or treated with an ‘equivalent’ dose of exogenous corticosterone (5 mg/kg, subcutaneously).We conclude that, in rats, repeated administration of EGB 761 prevents stress- and corticosterone-induced impairments of spatial memory.     

Positive impact of levetiracetam on emotional learning and memory in naive mice

AimsThe effect of an antiepileptic drug on cognitive function is of primary importance with respect to the patient's quality of life. Levetiracetam (LEV) is a novel antiepileptic drug used to treat epilepsy, but its effects on spatial and emotional learning and memory are not yet well understood. The goal of our study was to establish the effects of LEV (17 and 54 mg/kg, intraperitoneally (IP)) on spatial memory retrieval in the Morris water maze test and on acquisition and memory formation in the passive avoidance (PA) test in naive mice.Main methodsThe subjects were adult male BALB/c mice. Spatial learning and memory was established with the Morris water maze (MWM) test. The ‘time spent in escape platforms quadrant’ and the ‘distance to platform’ analyses were measured using a video tracking system to determine spatial memory function. Emotional learning and memory were determined with a one-trial, step-through passive avoidance test.Key findingsIn the MWM test, LEV (17 and 54 mg/kg) neither affected the time spent in the target quadrant nor altered the distance to platform. Moreover, LEV had no effect on swim speed. In the PA task, LEV (17 and 54 mg/kg) significantly prolonged retention latency.SignificanceOur results indicate that LEV did not alter spatial memory retrieval in the MWM test, but it did show some ameliorating effects on acquisition and memory formation in the PA test in naive mice.     

Changes in HPA reactivity and noradrenergic functions regulate spatial memory impairments at delayed time intervals following cerebral ischemia

This study investigates the association of ischemia-induced spatial memory impairment to alterations of the HPA axis and noradrenergic activation post insult. Experiment 1 characterized the effects of 10 min forebrain ischemia on corticosterone (CORT) secretion following ischemia and in response to spatial memory assessment in the Barnes maze, as well as the impact of pre-ischemia treatment with the glucocorticoid inhibitor metyrapone (175 mg/kg; s.c.). The results showed that cerebral ischemia represents a significant physiological stressor that upregulated CORT secretion 1, 24 and 72 h post-ischemia but not at 7 days. In response to testing in the Barnes maze ischemic animals showed elevated CORT secretion simultaneously with spatial memory deficits. The single dose of metyrapone attenuated the ischemia-induced adrenocortical hyper-responsiveness and subsequent memory deficits despite not providing neuroprotection in the hippocampal CA1 pyramidal cells. To complement these findings, we examined whether norepinephrine which provides positive feedback to the HPA axis and is upregulated following brain ischemia could influence memory performance at delayed intervals after ischemia. Experiment 2 demonstrated that pre-testing administration of the alpha2-adrenoceptor agonist clonidine (.04 mg/kg, s.c.) attenuated ischemia-induced working memory impairments in a radial maze while opposite effects were obtained with the antagonist yohimbine (.3 mg/kg, s.c.). Post-testing administration of clonidine produced spatial reference memory impairments in ischemic rats. The findings from the current study demonstrate increased sensitization and responsiveness of systems regulating stress hormones at long intervals post ischemia. Importantly, we demonstrate that these effects contribute to post ischemic cognitive impairments which can be attenuated pharmacologically even in the presence of hippocampal degeneration at time of testing.     

Individual and Combined Effects of Arsenic and Lead on Behavioral and Biochemical Changes in Mice

Arsenic (As) toxicity has caused an environmental tragedy affecting millions of people in the world. Little is known about the toxic effects of As on neurobehavioral and biochemical changes in vivo. Along this line of metal toxicity, co-exposure of lead (Pb) could aggravate the situation in the host. The present study was designed to explore the combined effects of As and Pb on behavioral changes like anxiety, spatial memory and learning impairment, and blood indices related to organ dysfunction. Exposure of mice to As (10 mg/kg body weight), Pb (10 mg/kg body weight), and As + Pb via drinking water significantly decreased the time spent exploring the open arms while it increased the time spent in the closed arms compared to control mice in the elevated plus maze. The mean latency time of the control group to find the platform decreased significantly during the learning for 7 days compared to all three treated groups in the Morris water maze test, and the As-exposed group spent significantly less time in the desired quadrant as compared to the control group in the probe trial. Both metals posed an anxiety-like behavior and deficits in spatial memory and learning, and also altered blood indices related to liver and kidney dysfunction, and a combined exposure of these metals inhibited the individual accumulation of As and Pb. Taken together, these data suggest that As has more toxic effects on neurobehavioral and biochemical changes than Pb, and there may be antagonism in the effects and accumulation between these two toxicants.     

Perinatal exposure to bisphenol-A impairs learning-memory by concomitant down-regulation of N-methyl-d-aspartate receptors of hippocampus in male offspring mice

Bisphenol-A (BPA) has been shown to influence development of the brain and behaviors. The purpose of the present report was to investigate the effects of perinatal exposure to BPA on learning/memory and its mechanism of action, especially focusing on N-methyl-d-aspartate receptor (NMDAR). Perinatal maternal exposure to BPA at 0.5, 5, and 50 mg/kg/d significantly extended the escape length to find the hidden platform in Morris water maze, and BPA at 0.5 or 5 mg/kg/d markedly decreased the percentage of time spent in the quadrant where the platform had been during training both in postnatal day (PND) 21 and PND 56 mice. The results of passive avoidance test showed that the error frequency to step down from a platform after received footshock was significantly increased, and the latency of the step-down response onto the grid floor 24 h after received footshock was obviously reduced by exposure to BPA at 5 and 50 mg/kg/d (P < 0.01) in the PND 21 offspring or at 50 mg/kg/d in the PND 56 offspring (P < 0.01). Furthermore, perinatal exposure to BPA significantly inhibited the expressions of NMDAR subunits NR1, NR2A, and 2B in the hippocampus during the development stage, especially in PND 56 mice. The expressions of estrogen receptor beta (ERβ) in both PND 21 and PND 56 mice were markedly down-regulated by BPA at 0.5, 5, and 50 mg/kg/d. These results indicate that perinatal exposure to BPA affects normal behavioral development in both spatial memory and avoidance memory, and also permanently influences the behavior of offspring in adulthood. The inhibition of expressions of NMDAR subunits and ERβ in hippocampus during postnatal development stage may be involved.     

Effects of uterine and lactational exposure to di-(2-ethylhexyl) phthalate on spatial memory and NMDA receptor of hippocampus in mice

Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disrupter. Currently, little is known about neurodevelopmental toxicity of DEHP in wildlife and humans. The present study investigated the effects of DEHP, focusing on the changes in the behavior of offspring mice at the ages of 6 and 12 w, respectively, following utero and lactational exposure to DEHP (10, 50, and 200 mg/kg/d) from gestation day 7 through postnatal day 21. The results of open field tasks showed that DEHP increased the grooming of males at age 6 w and females at age 12 w but decreased the frequency of rearing of 6-w-old females and the number of grid crossings of 12-w-old females. In the Morris water maze task, 50 and 200 mg/kg/d DEHP significantly prolonged the time of searching the hidden platform in water maze and reduced the time staying in the target quadrant during a probe trial of 6-w-old male mice, but not of 6-w-old females nor 12-w-old mice of both sexes, suggesting an impaired spatial learning and memory among younger males after perinatal exposure to DEHP. Western blot analyses further showed that DEHP at 50 and 200 mg/kg/d decreased the levels of the N-methyl-d-aspartic acid (NMDA) receptor subunits NR1 and NR2B in the hippocampus of 6-w-old males. These results suggest that uterine and lactational exposure to low doses of DEHP sex-specifically impacted behaviors, including locomotion activity and spatial memory, via the concomitant inhibition of the NMDA receptor of the hippocampus in offspring mice.     

Effects of a memory enhancing peptide on cognitive abilities of brain-lesioned mice: additivity with huperzine A and relative potency to tacrine.

Alzheimer's disease (AD) and related dementing disorders having cognitive manifestations represent an increasing threat to public health. In the present study, the effects of a memory enhancing NLPR tetra-peptide (MEP), huperzine A (Hup A), or a combination of the two on the cognitive abilities of brain-lesioned mice were evaluated and compared with tacrine in the passive avoidance and Y-water maze tests for the acquisition and retention aspects of cognitive functions. MEP at microg kg(-1) doses, and Hup A or tacrine at mg kg(-1) doses significantly reversed the cognition deficits induced by scopolamine. For acquisition ability, it was observed that mice administered with MEP (4.0 microg kg(-1)) spent less time escaping onto the platform in the water maze than those treated with tacrine (1.5 mg kg(-1)); whereas for memory retention, tacrine-administration resulted in a higher step-through latency in mice at the tested dose regime. In addition, co-administration of MEP (2.0 microg kg(-1)) and Hup A (0.1 mg kg(-1)) exhibited an additive effect resulting in considerable improvements in both acquisition and retention abilities of brain-lesioned mice. The results demonstrated that MEP was highly efficient in the rescue of cognitive abilities of brain-lesioned mice and in particular, the effective doses of MEP were about two orders of magnitude lower than that of tacrine, a therapeutic currently used in the treatment of AD. Moreover, MEP and Hup A were effective at reduced doses when the two were co-administered, providing a rationale for their combined usage in the treatment of cognitive deficits.     

Involvement of reduced acetylcholine release in Delta9-tetrahydrocannabinol-induced impairment of spatial memory in the 8-arm radial maze

To clarify the mechanism by which Delta9-tetrahydrocannabinol, a major psychoactive component of marijuana, impairs spatial memory in the 8-arm radial maze in rats via the cholinergic system, we used two acetylcholinesterase inhibitors, physostigmine and tetrahydroaminoacridine. Moreover, we examined the effect of Delta9-tetrahydrocannabinol on acetylcholine release in the frontal cortex and dorsal and ventral hippocampus using in vivo microdialysis. Physostigmine (0.01-0.05 mg/kg, i.p.) and tetrahydroaminoacridine (1-5 mg/kg, p.o.) improved the impairment of spatial memory induced by Delta9-tetrahydrocannabinol (6 mg/kg, i.p.) in the 8-arm radial maze. Delta9-tetrahydrocannabinol (6 mg/kg, i.p.) produced a significant decrease in acetylcholine release in the dorsal hippocampus as assessed by microdialysis. Moreover, tetrahydroaminoacridine at a dose of 1 mg/kg, which improved the impairment of spatial memory, reversed the decrease in acetylcholine release induced by Delta9-tetrahydrocannabinol in the dorsal hippocampus during 60-120 min after the Delta9-tetrahydrocannabinol injection. These findings suggest that inhibition of the cholinergic pathway by reduced acetylcholine release is one of the means by which Delta9-tetrahydrocannabinol impairs spatial memory in the 8-arm radial maze.     

The multi-herbal formula Chong-Myung-Tang improves spatial memory and increases cell genesis in the dentate gyrus of aged mice

Chong-Myung-Tang (CMT) is a multi-herbal formula that has been used to improve memory. However, the potential mechanism remains unknown. The present study investigated the effects of CMT (50, 100, and 200?mg/kg) on spatial memory of aged mice. The behavioral training tests indicated that 200?mg/kg CMT treatment can significantly improve spatial memory of aged mice in the Morris water maze. Moreover, cell survival was examined by injecting bromodeoxyuridine (BrdU) on the first three days. The result showed that 200?mg/kg CMT treatment significantly increased cell survival in the dentate gyrus. Cell proliferation was determined by injecting BrdU 2?h before the mice were killed. The result suggested that CMT treatments had no influence on cell proliferation in the dentate gyrus. Thus, an increase in cell survival in the dentate gyrus stimulated by CMT may be involved in the effect of CMT on spatial memory improvement.     

ESP-102, a standardized combined extract of Angelica gigas, Saururus chinensis and Schizandra chinensis, significantly improved scopolamine-induced memory impairment in mice

We assessed the effects of oral treatments of ESP-102, a standardized combined extract of Angelica gigas, Saururus chinensis and Schizandra chinensis, on learning and memory deficit. The cognition-enhancing effect of ESP-102 was investigated in scopolamine-induced (1 mg/kg body weight, s.c.) amnesic mice with both passive avoidance and Morris water maze performance tests. Acute oral treatment (single administration prior to scopolamine treatment) of mice with ESP-102 (doses in the range of 10 to 100 mg/kg body weight) significantly reduced scopolamine-induced memory deficits in the passive avoidance performance test. Another noteworthy result included the fact that prolonged oral daily treatments of mice with much lower amounts of ESP-102 (1 and 10 mg/kg body weight) for ten days reversed scopolamine-induced memory deficits. In the Morris water maze performance test, both acute and prolonged oral treatments with ESP-102 (single administration of 100 mg/kg body weight or prolonged daily administration of 1 and 10 mg/kg body weight for ten days, respectively, significantly ameliorated scopolamine-induced memory deficits as indicated by the formation of long-term and/or short-term spatial memory. In addition, we investigated the effects of ESP-102 on neurotoxicity induced by amyloid-beta peptide (Abeta25-35) or glutamate in primary cultured cortical neurons of rats. Pretreatment of cultures with ESP-102 (0.001, 0.01 and 0.1 mug/ml) significantly protected neurons from neurotoxicity induced by either glutamate or Abeta25-35. These results suggest that ESP-102 may have some protective characteristics against neuronal cell death and cognitive impairments often observed in Alzheimer's disease, stroke, ischemic injury and other neurodegenerative diseases.