石杉碱甲对樟柳碱所致动物记忆障碍的改善作用

采用步下法和步入法观察石杉碱甲对樟柳碱所致记忆障碍的改善作用。结果表明,樟柳碱可使动物步下平台和步入暗箱的潜伏期明显缩短,错误次数增加以及错误反应动物的百分数增加。石杉碱甲对樟柳碱所致的记忆障碍有一定的改善作用:石杉碱甲可使动物步下平台的潜伏期明显延长;使动物步入暗箱的潜伏期延长、错误次数减少以及错误动物的百分数减少。     

几种促智药对樟柳碱所致记忆障碍的改善作用

采用跳台法和避暗法观察中医秘方ＴＣＭ９０１和ＴＣＭ９０２以及脑复智和尼莫地平对樟柳碱所致记忆障碍的改善作用。结果表明,它们均可较好地改善记忆障碍。使动物下跳台或步入暗箱的潜伏期明显延长,并使它们的错误次数明显减少。结果还提示,ＴＣＭ９０１和ＴＣＭ９０２的作用与脑复智和尼莫地平相比,效果几乎相仿,但其中ＴＣＭ９０２的效果似乎更好。     

放射性钍对狗迷路瞬时记忆的影响

本工作在四只狗上建立了延缓条件反应,观察体内电离辐射对动物学习记忆的影响。结果显示,静脉注射放射性硝酸钍,剂量为每次10毫克/公斤体重,每日一次;总注入量平均8.68克,超过允许剂量350倍;没有引起延缓条件反应的明显障碍。这表明狗的瞬时记忆对于放射性灶电离辐射的耐受力是比较强的。     

抑制儿茶酚胺的生物合成对群体隔离大白鼠学习和记忆的影响

本文观察了儿茶酚胺的生物合成抑制剂——α-甲基酪氨酸(α-MT)和二乙基二硫氨基甲酸酯钠(DDC)——对群体隔离大白鼠学习和记忆的影响。结果发现α-MT(250mg/公斤体重)对群居动物学习方位水迷津无明显影响,但对隔离动物的学习有明显影响。α-MT对群居和隔离动物的记忆的影响不明显,DDC(500mg/公斤体重)对群居和隔离动物的学习和记忆均无明显影响。注射α-MT后隔离动物大脑皮质内去甲肾上腺素的含量降低了38.1％,而群居动物仅降低了20.1％。结果提示隔离动物对方位水迷津学习能力的降低可能与脑内去甲肾上腺素和多巴胺的含量下降尤其是与大脑皮质内去甲肾上腺素含量的下降有关。     

樟柳碱对动物分辨学习、记忆行为和电活动的影响

樟柳碱是我国首先提取出的一种生物碱,它的作用和东莨菪碱相似,而其毒性较小,但如过量服用会引起幻觉和认知障碍。本文观察了樟柳碱对大白鼠分辨学习和记忆行为的影响,并探讨樟柳碱对家兔脑皮层的自发和诱发电活动以及脑皮层电图条件反应的影响。其主要结果如下: 樟柳减对大白鼠的分辨学习和记忆有较明显的影响,其主要表现为错误反应增多,反应时延长以及防御性条件反射的出现率低。 樟柳碱能使家兔全皮层出现高振幅慢波,并能使脑皮层电图条件反应受到明显的抑制。     

次声对小鼠记忆的破坏作用

次声具有独特的物理性质,它是一种人耳听不到的声音。在一定的条件下,它对人体的生理和心理功能有伤害。本文旨在探讨次声对动物记忆的影响。结果表明,在实验条件下,次声对动物的记忆有一定的破坏作用。在次声作用下,小鼠步入暗箱或步下平台的潜伏期缩短或明显缩短。并且,它们的错误次数增加或明显增加。     

预警、重复学习和反馈对错误记忆的影响——错误记忆的信号检测论分析

本研究用信号检测论分析预警、重复学习和反馈三种变量对错误记忆的影响.实验1考察预警指导语的影响.实验2考察重复学习和反馈的影响.结果表明:预警对被试辨别力和反应偏向的影响不明显,对错误记忆影响也不显著;重复学习不能明显影响被试的反应标准,但可提高辨别力减弱错误记忆;反馈明显使被试倾向于使用更为宽松的反应标准,难以降低错误记忆.再认双加工模型和激活/监测理论能对实验结果做出合理的解释.     

环境雌激素双酚A对成年小鼠学习记忆和突触结构的影响*

双酚A (bisphenol, BPA)是一种广泛存在的环境内分泌干扰物,它可与雌激素受体结合干扰内源性雌激素对中枢神经系统的调控作用。本研究通过将10周龄小鼠灌胃染毒BPA (0.4、4、40 mg/kg/day)3个月,研究长期BPA暴露对成年小鼠记忆行为和突触可塑性的影响。开场行为测试结果表明, BPA (0.4、4、40 mg/kg/day)增加雄性的站立次数和理毛频率, BPA (4 mg/kg/day)却显著减少雌鼠的站立次数。水迷宫和被动回避行为模型检测显示, BPA主要损伤雄鼠的空间学习记忆和被动回避记忆。通过制备海马CA1区超薄切片后,电镜观测发现, BPA (0.4、40 mg/kg/day)暴露降低雄鼠海马CA1区突触数密度,缩短雄鼠突触前活性带长度,减小雄鼠突触后致密体(PSD)厚度,增加雄鼠突触间隙宽度。进一步用Western blot方法检测突触前、后的标志性蛋白Synapsin I和PSD95以及兴奋性氨基酸NMDA受体NR1亚基和AMPA受体GluR1亚基蛋白的表达,发现BPA暴露致雄鼠Synapsin I、PSD95、NR1蛋白表达水平下调。而BPA对雌鼠的记忆行为、突触形态、突触蛋白和受体蛋白均没有明显作用。以上结果提示长期B PA暴露性别特异性地影响成年小鼠的活动性和探究行为,损伤雄鼠的学习记忆,这些作用可能通过下调突触蛋白和NMDA受体的表达而负性影响突触结构可塑性,最终影响雄鼠的学习记忆功能。     

血糖水平对STZ鼠探究行为及学习记忆的影响

为了解不同血糖水平下链脲佐菌素诱导鼠（STZ鼠）探究行为与学习和记忆的变化情况,把60只STZ鼠按血糖水平分成高血糖组、良好血糖组和低血糖组3组,进行延迟时间、探究时间测定和小鼠跳台试验,并与正常对照组比较。结果发现,良好血糖组与正常对照组各检测指标均相近;3组STZ鼠延迟时间、完成迷津作业时间均按血糖值递增;组间差异显著;小鼠跳台试验中高血糖组的错误数最多,24小时后错误数最少,前后差值有组间差异;延迟时间、探究时间与血糖呈显著正相关,错误数差值与血糖呈显著负相关。结果表明,高血糖鼠的探究行为和学习能力最差,但对被动回避学习的记忆保持相对较好。     

婴鼠丫迷津吸乳辨别学习行为的发展与脑生长和旋转行为关系的实验研究

0—20日龄Wistar婴鼠脑重增长速度曲线表示出“脑生长突发期”,并观察到曲线的高峰在10日龄附近。所完成的12—20日龄婴鼠Y迷津吸乳辨别学习行为发展的实验观察到,婴鼠学习行为水平的明显提高发生在16日龄(“脑生长突发期”的后期)。该结果表明婴鼠Y迷津学习行为的发展与脑生长之间存在密切关系。本实验证明,能被苯异丙胺(i.p.5mg/kg)诱发的旋转型婴鼠Y迷津学习行为表现优于不能被苯异丙胺诱发的非旋转型婴鼠,并发现与食物奖偿方向(R臂)相一致的R旋转型婴鼠学习行为表现最佳,此现象随婴鼠日龄的增长而明显。这暗示婴鼠左右方位辨别学习行为与大脑两半球机能不对称性有密切关系。     

围生期双酚A暴露对不同性别子代小鼠行为的影响

探讨围生期母体双酚A(bisphenol A, BPA)暴露对幼年期(生后21~30天, postnatal day 21~30, PND 21~30)和青年期(生后56~63天, PND 56~63)不同性别子代小鼠行为的影响。母鼠从妊娠第7天至断乳前(产后21天)进行BPA(0.05、0.5、5、50 mg/kg/day)灌胃染毒, 同时设对照组。每个剂量组分别在PND 21和PND 56开始测试雌雄子代小鼠各项行为。以旷场行为检测小鼠的自发活动及探究行为, 以高架十字迷宫检测小鼠的焦虑行为, 以水迷宫检测小鼠的空间学习记忆能力, 以跳台检测小鼠的被动回避记忆行为。结果表明, BPA使PND 21雌雄子鼠和PND 56雄性子鼠自发活动减少(p<0.05或p<0.01), 理毛和站立行为发生性别分化(p<0.05或p<0.01); PND 21子鼠的3分钟跑动格数有明显的剂量效应关系, 其中5~50 mg/kg/day组特别显著。BPA显著增加PND 21雌雄子鼠和PND56雌性子鼠在高架十字迷宫中进入开放臂次数和停留时间(p<0.05或p<0.01)并减少封闭臂的进入时间, 但没有明显的剂量效应关系; BPA减少PND 56雄性子鼠开放臂的进入并增加其封闭臂的进入, 干扰了幼年期和青年期小鼠焦虑行为的性别分化。BPA剂量依赖性地延长PND 21和PND 56雄性子鼠在水迷宫搜索平台的平均距离, 其中5~50 mg/kg/day剂量组具有差异显著性(p<0.05或p<0.01), 但对雌性子鼠空间学习记忆行为没有影响。此外, 5~50 mg/kg/day BPA增加PND 21雄性子鼠在跳台实验中的错误次数并缩短其跳下平台潜伏期, PND 56雌雄子鼠的被动回避记忆仅被50 mg/kg/day BPA减弱。以上结果提示, 围生期BPA暴露可影响子代小鼠幼年期和青年期的多种行为及行为的性别差异, 不同行为对BPA的敏感程度不同, 其中以自发活动和探究行为最敏感。     

The ameliorating effect of oroxylin A on scopolamine-induced memory impairment in mice

Oroxylin A is a flavonoid and was originally isolated from the root of Scutellaria baicalensis Georgi., one of the most important medicinal herbs in traditional Chinese medicine. The aim of this study was to investigate the ameliorating effects of oroxylin A on memory impairment using the passive avoidance test, the Y-maze test, and the Morris water maze test in mice. Drug-induced amnesia was induced by administering scopolamine (1 mg/kg, i.p.) or diazepam (1 mg/kg, i.p.). Oroxylin A (5 mg/kg) significantly reversed cognitive impairments in mice by passive avoidance and the Y-maze testing (P<.05). Oroxylin A also improved escape latencies in training trials and increased swimming times and distances within the target zone of the Morris water maze (P<.05). Moreover, the ameliorating effects of oroxylin A were antagonized by both muscimol and diazepam (0.25 mg/kg, i.p., respectively), which are GABA(A) receptor agonists. Furthermore, oroxylin A (100 microM) was found to inhibit GABA-induced inward Cl(-) current in a single cortical neuron. These results suggest that oroxylin A may be useful for the treatment of cognitive impairments induced by cholinergic dysfunction via the GABAergic nervous system.     

Radial arm maze performance of mice: acquisition and atropine effects

CD-1 mice were successfully trained in a six-arm radial maze in which half of the arms were baited, a procedure which had been used to differentiate between reference and working memory. Stable performance was achieved following eight daily training sessions, as measured by decreasing running time and number of errors. This finding strengthens the foraging hypothesis as a basis for the performance of rodents in the radial maze. Acute subcutaneous administration of the cholinergic antagonist atropine sulfate (1-6 mg/kg) to trained mice produced dose-related increases in running time and working memory errors, with a slight decrease in reference memory errors. This is in agreement with other studies on the role of the cholinergic system in memory processes. The peripheral cholinergic blocker, atropine methyl nitrate (4 mg/kg), somewhat increased running time without decreasing performance accuracy. In contrast to the prolonged pharmacological and physiological effects of atropine, behavioral decrements disappeared within 3 hr. It is concluded that mice trained in the radial arm maze may be used for screening of the effects of drugs on cognitive function.     

Genistein ameliorates learning and memory deficits in amyloid β(1-40) rat model of Alzheimer's disease

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by increased β-amyloid (Aβ) deposition and neuronal dysfunction leading to impaired learning and recall. Ageing, heredity, and induced oxidative stress are among proposed risk factors. The increased frequency of the disease in women also suggests a role for estrogen in development of AD. In the present study, effects of the phytoestrogen genistein (10mg/kg) on learning and memory impairments was assessed in intrahippocampal Aβ(1-40)-injected rats. The estrogen receptor antagonist fulvestrant was injected intracerebroventricularly in a group of Aβ-lesioned rats. The Aβ-injected animals exhibited the following: lower spontaneous alternation score in Y-maze tasks, impaired retention and recall capability in the passive avoidance test, and fewer correct choices and more errors in the RAM task. Genistein, but not genistein and fulvestrant, significantly improved most of these parameters. Measurements of oxidative stress markers in hippocampal tissue of Aβ-injected rats showed an elevation of malondialdehyde (MDA) and nitrite content, and a reduction of superoxide dismutase (SOD) activity. Genistein significantly attenuated the increased MDA content but did not affect the nitrite content or SOD activity. These results indicate that genistein pretreatment ameliorates Aβ-induced impairment of short-term spatial memory in rats through an estrogenic pathway and by inducing attenuation of oxidative stress.     

High-fat diets impair spatial learning in the radial-arm maze in mice

It has been suggested that hyperglycemia and insulin resistance triggered by energy-dense diets can account for hippocampal damage and deficits of cognitive behaviour. We wonder if the impairment of learning and memory processes detected in diet-induced obese (DIO) mice is linked to diet composition itself. With this purpose we have evaluated learning performance in mice undergoing a short-term high-fat (HF) treatment, which leads to a pre-obese state characterized by increased adiposity without significant changes of glucose and insulin plasma levels. C57BL/6J mice were fed either a HF (45 kcal% from fat) or control diet (10 kcal% from fat) during 8 weeks. Learning performance was evaluated by using the four-arm baited version of the eight-arm radial maze test (RAM). Mice were trained to learn the RAM protocol and then memory was tested at different time-points. Time spent to consume food placed in baited arms and errors committed to find them were measured in all sessions. DIO mice significantly spent more time in learning the task and made a greater number of errors than controls. Moreover, retention tests revealed that both working and total memory errors were also more numerous in DIO mice. The current results show that short-term DIO impairs spatial learning and suggest that impairment of hippocampal learning elicited by HF diets might be perceptible before metabolic alterations linked to obesity develop.     

Amnesia produced by anisomycin in an appetitive task is not due to conditioned aversion

Two experiments investigated the effects of lithium chloride (LiCl) and anisomycin (ANI) in a water reward Y-maze task. In Experiment 1, male CD-1 mice given weak or strong training were injected post-training with either saline or LiCl (150 mg/kg), which has been reported to produce conditioned aversion in mice. One day after training, both LiCl groups avoided the rewarded arm of the maze and drank less water than saline-injected controls. Two days after training, the strongly trained LiCl mice showed avoidance, while both LiCl groups drank less water. In Experiment 2, weakly trained mice given pre- and post-training ANI (30 mg/kg) were amnesic on the second test day compared to mice that received post-trial saline. However, water consumption was increased on the test day for both groups. LiCl produced a different pattern of results than ANI in this task. On the basis of these results, it is suggested that amnesia produced by ANI is due to impaired memory formation and not to conditioned aversion.     

Effects of ketamine on tunnel maze and water maze performance in the rat

The NMDA receptor, which has been implicated in memory formation, is noncompetitively blocked by ketamine. The present study examines the effect of ketamine (0, 3, 6, 12, and 25 mg/kg body wt; ip) on tunnel maze and water maze performance in Wistar rats. In the hexagonal tunnel maze (HTM) high doses of ketamine (12 and 25 mg/kg) decreased locomotor activity. Moreover, ketamine induced perimeter walking (6, 12, and 25 mg/kg) and attenuated exploratory efficiency (25 mg/kg). When the HTM was converted into a modified six-arm radial maze, ketamine impaired short-term but not long-term memory. In the Morris water maze, rats injected with ketamine (12 and 25 mg/kg) acquired a spatial navigation task more slowly than controls. When the escape platform was removed, the drug-treated rats did not preferentially search for it in the area where the platform had been during the acquisition phase. However, when the escape platform was visible, no differences in the performance of ketamine-treated and control rats could be found. In summary, ketamine seems to attenuate some but not all forms of learning in the tunnel maze and it impairs the acquisition of a spatial navigation task.     

The Effects of L-glucose on memory in mice are modulated by peripherally acting cholinergic drugs.

D-Glucose improves memory in animals and humans and in subjects with memory pathologies. To date, the accepted conclusion drawn from animal research is that D-glucose improves memory via alterations in central cholinergic systems. However, recent evidence suggests that a sugar which does not cross the blood-brain barrier also facilitates memory (Talley, Arankowsky-Sandoval, McCarty, & Gold, 1999). The present study examined the effects of peripherally administered L-glucose, a stereoisomer of D-glucose, in male mice. Intraperitoneal administration of L-glucose (300 mg/kg) before testing enhanced place learning in the Morris water maze. Mice injected with L-glucose had significantly shorter escape latencies than mice injected with saline (1 ml/kg). Effects were observed on both reference memory and working memory tasks. L-Glucose did not facilitate performance on either task when it was simultaneously administered with cholinergic antagonists that are excluded from the central nervous system. Thus, simultaneous administration of either methyl-scopolamine (0.3 mg/kg), a peripherally acting muscarinic receptor blocker, or hexamethonium (1 mg/kg), a peripherally acting nicotinic receptor blocker, reversed the effect of L-glucose on memory. These findings suggest that the memory effects of l-glucose may be mediated by facilitated acetylcholine synthesis and/or release in the peripheral nervous system.     

Cyclophosphamide impairs hippocampus-dependent learning and memory in adult mice: Possible involvement of hippocampal neurogenesis in chemotherapy-induced memory deficits

Cyclophosphamide (CYP) is an anti-neoplastic agent as well as an immunosuppressive agent. In order to elucidate the alteration in adult hippocampal function following acute CYP treatment, hippocampus-related behavioral dysfunction and changes in adult hippocampal neurogenesis in CYP-treated (intraperitoneally, 40 mg/kg) mice (8–10-week-old ICR) were analyzed using hippocampus-dependent learning and memory tasks (passive avoidance and object recognition memory test) and immunohistochemical markers of neurogenesis (Ki-67 and doublecortin (DCX)). Compared to the vehicle-treated controls, mice trained at 12 h after CYP injection showed significant memory deficits in passive avoidance and the object recognition memory test. The number of Ki-67- and DCX-positive cells began to decrease significantly at 12 h post-injection, reaching the lowest level at 24 h after CYP injection; however, this reverted gradually to the vehicle-treated control level between 2 and 10 days. We suggest that the administration of a chemotherapeutic agent in adult mice interrupts hippocampal functions, including learning and memory, possibly through the suppression of hippocampal neurogenesis.     

Extinction of appetitive learning is disrupted by cycloheximide and propranolol in the sand maze in rats

The present study investigated whether memory for extinction in an appetitive task (the sand maze) could be attenuated by administration of cycloheximide (protein synthesis inhibitor) or propranolol (β-adrenergic receptor antagonist). Ninety-day-old male Long-Evans rats were trained to retrieve a sweet cereal reinforcer from an open container in the sand maze. One day following this non-spatial training, rats received three extinction trials in which they were placed in the maze with the reinforcer present, but unattainable. Thirty minutes prior to the first extinction trial, rats received an intraperitoneal injection of cycloheximide (1mg/kg), propranolol (25mg/kg), or vehicle (1mg/kg distilled water). Twenty-four hours later, rats were tested in the sand maze with the reinforcer again available. Results from the test trial showed that both cycloheximide and propranolol groups found the reinforcer more quickly than controls. Two weeks later, rats were trained on a spatial version of the sand maze in which they had to search for a buried reinforcer using extramaze cues. Cycloheximide and propranolol groups learned this task significantly faster than the control group, demonstrating the long-lasting effect of cycloheximide and propranolol on the blocking of memory for extinction.