Time dependent changes in anterograde scopolamine-induced amnesia in rats

These experiments studied the effect of scopolamine on memory formation and subsequent memory recall. Different groups of rats were trained on a Y-maze brightness discrimination task 20 min after IP injection of 2 mg/kg scopolamine HBr, an anticholinergic. Retention tests were then conducted 1 day or 2, 4, or 6 weeks after training. Deficits in retention performance were observed at 1 day and 2 weeks after training but not at the longer intervals. In addition, other rats were trained in the same manner and after the same dose of scopolamine but were then retention tested 20 min after 0.5 mg/kg physostigmine salicylate, a cholinesterase inhibitor. These subjects also showed deficits at 1 day and 2 weeks but were not different from controls at the longer intervals. Amnesia was not, however, produced after treatment with scopolamine methyl nitrate or by injections of scopolamine HBr administered immediately after training. These results suggest that scopolamine, present in the central nervous system during training or within the first few moments thereafter, modifies the formation of the memory trace in such a way that memory is not available for recall for a period of weeks.     

喹硫平合并石杉碱甲治疗精神分裂症患者记忆功能障碍的临床观察

目的探讨喹硫平联合石杉碱甲治疗精神分裂症患者记忆认知功能障碍的疗效。方法将60例精神分裂症患者随机分成两组,每组各30例,喹硫平联合石杉碱甲治疗（合用组）和单独服用喹硫平（对照组）,疗程为12周。分别于治疗前及治疗2、6、12周采用阳性与阴性症状量表（PANSS）和韦氏记忆量表修订本测评记忆功能,并记录不良反应的情况。结果合用组在治疗第6周后记忆功能即有显著改善,对照组治疗前后变化不明显;治疗第12周后,合用组较对照组记忆商总分比较差异有统计学意义,合用组显效率高于对照组,两组总的不良反应较轻。结论石杉碱甲有助于改善精神分裂症患者的记忆功能。     

二苯乙烯苷对慢性脑缺血大鼠学习记忆的影响

目的观察何首乌有效成分二苯乙烯苷(TSG)对慢性脑缺血大鼠学习记忆能力的影响,并探讨其可能机制。方法雄性SD大鼠双侧颈总动脉永久性结扎制备慢性脑缺血致痴呆模型。术前2周起,分别给TSG30,60及120mg·kg-1·d-1,ig,连续11周。术后8周时,分别用Morris水迷宫实验和避暗实验检测大鼠的空间学习记忆能力和被动回避学习记忆能力。术后9周时,采用生化方法检测海马乙酰胆碱酯酶(AChE)活性,免疫组化方法检测海马蛋白磷酸酶2A(PP-2A)和微管相关蛋白2(MAP-2)的表达。结果慢性脑缺血模型组大鼠空间和被动回避学习记忆能力明显降低,海马AChE活性显著升高,PP-2A和MAP-2表达明显减少。TSG给药10周可显著改善慢性脑缺血引起的学习记忆能力降低;给药11周明显抑制海马AChE活性增高,并增加PP-2A和MAP-2的表达。结论TSG可改善慢性脑缺血大鼠的学习记忆能力,其机制可能与抑制海马AChE活性,增加海马PP-2A和MAP-2的表达有关。     

Intranasal insulin improves memory in humans: superiority of insulin aspart.

There is compelling evidence that intranasal administration of regular human insulin (RH-I) improves memory in humans. Owing to the reduced tendency of its molecules to form hexamers, the rapid-acting insulin analog insulin aspart (ASP-I) is more rapidly absorbed than RH-I after subcutaneous administration. Since after intranasal insulin administration, ASP-I may also be expected to access the brain, we examined whether intranasal ASP-I has stronger beneficial effects on declarative memory than RH-I in humans. Acute (40 IU) and long-term (4 x 40 IU/day over 8 weeks) effects of intranasally administered ASP-I, RH-I, and placebo on declarative memory (word lists) were assessed in 36 healthy men in a between-subject design. Plasma insulin and glucose levels were not affected. After 8 weeks of treatment, however, word list recall was improved compared to placebo in both the ASP-I (p<0.01) and the RH-I groups (p<0.05). ASP-I-treated subjects performed even better than those of the RH-I-treated group (p<0.05). Our results indicate that insulin-induced memory improvement can be enhanced by using ASP-I. This finding may be especially relevant for a potential clinical administration of intranasal insulin in the treatment of memory disorders like Alzheimer's disease.     

Protective effects of chronic lithium treatment against spatial memory retention deficits induced by the protein kinase AII inhibitor H-89 in rats

We have previously shown that infusion of the PKAII inhibitor H-89 in the CA1 area of the hippocampus impaired spatial memory retention. There is some evidence suggesting the neuroprotective effects of chronic lithium administration including its ability to attenuate a deleterious effect of chronic stress on spatial memory in rats. In the present study, we investigated whether chronic administration of lithium can improve memory as well as influence the inhibitory effect of H-89 on spatial memory retention. Male albino rats were treated systemically with lithium (600 mg/l) for 4 weeks and then trained for 4 days in the Morris water maze. Testing the animals 48 h later showed a significant reduction in escape latency (p < 0.05) and travel distance (p < 0.05) compared to the controls. In separate experiments, the rats were similarly treated with lithium for 4 weeks, followed by similar training for 4 days and then immediately infused bilaterally with vehicle or 5 micromol/l H-89 into the CA1 region of the hippocampus. Animals were then tested 48 h after H-89 infusion in order to assess their spatial memory retention. The lithium treatment caused a significant reduction in escape latency (p < 0.001) and travel distance (p < 0.001) compared to H-89-treated animals. The data suggest that lithium treatment for 4 weeks improved spatial memory retention and that lithium pretreatment prevented or reversed the H-89-induced spatial memory deficits.     

Learning and Memory of Rats after Long-Term Administration of Low Doses of Parathion

A set of four learning and memory tests (Morris Maze I for referencememory, Morris Maze II for working memory, one-way active avoidance,and passive avoidance) were employed to address the questionswhether parathion impaired cognitive functions after low, long-termexposure and could cause persistent changes in cognition. Motoractivity and general behavior were investigated in a functionalobservational battery. Parathion was administered in rat foodin low doses which caused no clinical symptoms and no or borderlinebrain acetylcholinesterase inhibition. Parathion doses of 0.5,2, or 8 ppm in rat food produced the averaged uptake of 24,100, or 400 µg/kg body weight per group per day in malerats and 36, 152, or 550 µg/kg per day in female ratsin week 13. Learning tests were performed in weeks 1 to 4 and10 to 14, as well as 30 to 34 weeks after the end of treatment,when the male and female rats were about 13 months old. Lowdoses of parathion given daily for 13 weeks had no cumulativeor adverse effects on learning and memory, either during treatmentor after the extended treatment-free period, in any of the tests.A significant improvement of learning compared to control observedin the Morris Water Maze I during the first week of treatment(males dose group 0.5 ppm) shows that parathion can improvedcognitive functions in rats. Results of the study indicate thatadverse effects changing learning and memory in animals mayoccur only at higher doses of organophosphates, at which theperipheral and brain acetylcholinesterases are inhibited toa greater extent than those in the present Study.     

Chronic nicotine working and reference memory effects in the 16-arm radial maze: interactions with D1 agonist and antagonist drugs

Chronic nicotine infusion has been found in a series of studies in our laboratory to significantly improve choice accuracy of rats in the eight-arm radial maze. The current study was designed to compare the effects of chronic nicotine infusion on working and reference memory in a 16-arm radial maze. Nicotine was administered to female Sprague-Dawley rats at approximately 5 mg/kg per day SC via osmotic minipumps. Controls received saline infusions. Chronic nicotine infusion significantly lowered the number of working memory errors compared to controls, whereas the number of reference memory erros was not significantly affected. The modest nicotine-induced reduction in working memory errors was seen as a main effect over the 4 weeks of infusion, but the clearest effect was seen in weeks 3–4 of nicotine administration. For the 2 weeks after withdrawal, the nicotine effect was no longer evident. Acute D₁ challenges were given with the D₁ agonist dihydrexidine (0, 0.25, 0.5 and 1 mg/kg) and the D₁ antagonist SCH 23390 (0, 0.005, 0.015 and 0.05 μg/kg) during weeks 3–4 of chronic nicotine administration and weeks 1–2 after withdrawal from nicotine. Dihydrexidine caused a modest dose-related increase in reference memory errors but not working memory errors in the nicotine-treated, but not the control rats. The D₁ antagonist SCH 23390 caused a modest though significant decrease in reference memory errors but not working memory errors in the control, but not the nicotine-treated rats. The behavioral specificity of chronic nicotine infusion was demonstrated with selective improvement in working memory function. Pharmacological interactions were seen with chronic nicotine treatment increasing responsivity to D₁ agonist and decreasing responsivity to a D₁ antagonist with regard to reference memory. The mechanisms of this interaction are still undiscovered.     

镍钛记忆合金环抱形肋骨接骨板治疗无连枷胸多发肋骨骨折对呼吸功能的影响

目的探索镍钛记忆合金环抱形肋骨接骨板治疗无连枷胸的多发肋骨骨折对呼吸功能的影响。方法将该院自2009年3～2011年3月同期收治的109例多发肋骨骨折患者分为内固定手术组和保守治疗组进行了回顾性研究,主要观察患者呼吸功能变化情况。结果伤后两周手术治疗组肺功能稍好,但差异无显著性,血气差异亦无统计学意义,P0.05;半年后肺功能差异有显著意义,P0.01,血气差异仍无统计学意义,P0.05。结论肋骨环抱接骨板内固定治疗多发肋骨骨折是一种简便安全的手术方法,虽然对伤后两周呼吸功能不能明显改善,但可以提高患者的远期呼吸功能。     

Intracortical AF64A: memory impairments and recovery from cholinergic hypofunction

The long-term effects of intracortical AF64A (ethylcholine mustard aziridinium ion) treatment on presynaptic cortical cholinergic markers and cognitive function in the rat were investigated. Two 1.0 microliter infusions of AF64A (1 nmole/microliter) or vehicle were placed bilaterally into the fronto-parietal cortex. At 3 weeks postinfusion, AF64A-treated animals were found to be deficient in passive avoidance memory retention. During weeks 4 through 10, AF64A-treated animals were markedly deficient in the extinction (memory) phase, but not the acquisition (learning) phase of 2-way active avoidance behavior. Cortical acetylcholine synthesis and high-affinity choline uptake were significantly decreased in AF64A-treated animals at 24 hours, 3 weeks, and 10 weeks following infusion. At 6 months after AF64A treatment, however, cortical cholinergic markers were not reduced compared to controls. These data indicate that memory deficits are observed during a period of cortical cholinergic hypofunction induced by cortical AF64A infusions and that a recovery from such hypofunction occurs by 6 months after these infusions.     

十全大补汤对D-半乳糖模型小鼠学习记忆及抗氧化的研究

目的十全大补汤对D-半乳糖致衰老小鼠学习记忆能力及抗氧化作用的研究。方法连续给小鼠注射D-半乳糖6周,同时从第三周起给模型鼠灌胃十全大补汤,给药结束后,进行学习记忆行为测定,采血清测定超氧化歧化酶（SOD）、丙二醛（MDA）含量。结果十全大补汤组小鼠的学习、记忆获得和记忆消退的错误次数明显少于衰老模型组（P〈0．05）;与模型组比较,十全大补汤组小鼠血清SOD活性显著性降低。结论十全大补汤能改善D-半乳糖致衰老小鼠的学习记忆能力,提高体内SOD活性,增强其对自由基的清除能力,抑制脂质过氧化作用。     

Chronic administration of docosahexaenoic acid improves the performance of radial arm maze task in aged rats

1. In the present study, we investigated the effect of docosahexaenoic acid (DHA) on spatial memory related learning ability in aged (100 weeks) male Wistar rats. 2. Rats were fed a fish oil-deficient diet through three generations and were then randomly divided into two groups. Over 10 weeks, one group was per orally administered 300 mg/kg per day DHA dissolved in 5% gum Arabic solution and the other group was administered the vehicle alone. Five weeks after the start of the administration, rats were tested with the partially baited eight-arm radial maze to estimate two types of spatial memory related learning ability displayed by reference memory error and working memory error. 3. Chronic administration of DHA significantly decreased the number of reference memory errors and working memory errors. 4. The level of lipid peroxide (LPO) in the hippocampus tended to decrease with chronic DHA administration and demonstrated a positive correlation with the number of reference memory errors. 5. These results suggest that the accumulation of hippocampal LPO reduces spatial memory related learning ability in aged rats. Moreover, chronic administration of DHA was effective in decreasing the level of hippocampal LPO, then improving learning ability.     

Effects of intracerebroventricular administration of ethylcholine aziridinium ion on hippocampal cholinergic system,assayed in vivo by a brain dialysis technique,and on spatial memory of rats

We attempted to clarify the effect of hippocampal function on the spatial memory of rats by creating a lesion in the hippocampus with ethylcholine aziridinium ion (AF64A). The hippocampus was damaged by injecting AF64A into the lateral ventricles, 3 nmol/3 μl per side. At 1 or 4 weeks after the injection, acetylcholine (ACh) was measured in perfusion samples collected via brain dialysis of the hippocampus of freely moving rats. The release of ACh stimulated by scopolamine was reduced at 1 week but not at 4 weeks post-injection. A behavioral change on the eight-arm radial maze test was also observed in the acquisition or retention trials to determine the deficit in spatial memory, whether acquisition or retention. In the acquisition trial, the initial correct response was decreased and the total error count was increased at 1.5 to 2.5 weeks, but not at 3 weeks, after the AF64A injection. However, those indices remained unchanged in the retention trial. These observations suggest that the hippocampus may be required for the acquisition of spatial memory, but that the stored memory, but the stored memory is located outside the hippocampus, the hippocampus is not concerned with the retrieval process, or the retrieval process may be hippocampal but not cholinergic. The hippocampal cholinergic system would be concerned with the acquisition of spatial memory. Thus, AF64A-treated rats may serve a model for hippocampal cholinergic dysfunction and the recovery from hippocampal cholinergic damage. © 1993 Wiley-Liss, Inc.     

Differential cognitive effects of <Emphasis Type="Italic">Ginkgo biloba</Emphasis> after acute and chronic treatment in healthy young volunteers

Rationale Acute doses of Ginkgo biloba have been shown to improve attention and memory in young, healthy participants, but there has been a lack of investigation into possible effects on executive function. In addition, only one study has investigated the effects of chronic treatment in young volunteers.Objectives This study was conducted to compare the effects of ginkgo after acute and chronic treatment on tests of attention, memory and executive function in healthy university students.Methods Using a placebo-controlled double-blind design, in experiment 1, 52 students were randomly allocated to receive a single dose of ginkgo (120 mg, n=26) or placebo (n=26), and were tested 4 h later. In experiment 2, 40 students were randomly allocated to receive ginkgo (120 mg/day; n=20) or placebo (n=20) for a 6-week period and were tested at baseline and after 6 weeks of treatment. In both experiments, participants underwent tests of sustained attention, episodic and working memory, mental flexibility and planning, and completed mood rating scales.Results The acute dose of ginkgo significantly improved performance on the sustained-attention task and pattern-recognition memory task; however, there were no effects on working memory, planning, mental flexibility or mood. After 6 weeks of treatment, there were no significant effects of ginkgo on mood or any of the cognitive tests.Conclusions In line with the literature, after acute administration ginkgo improved performance in tests of attention and memory. However, there were no effects after 6 weeks, suggesting that tolerance develops to the effects in young, healthy participants.     

Eating soya improves human memory

RATIONALE: Soya foods are rich in isoflavone phytoestrogens with weak agonist activity at oestrogen receptors. Oestrogen treatment has been found to improve memory in men awaiting gender reassignment and in post-menopausal women. OBJECTIVE: To examine the effects of supervised high versus low soya diets on attention, memory and frontal lobe function in young healthy adults of both sexes. METHODS: Student volunteers were randomly allocated to receive, under supervision, a high soya (100 mg total isoflavones/day) or a low soya (0.5 mg total isoflavones/day) diet for 10 weeks. They received a battery of cognitive tests at baseline and then after 10 weeks of diet. RESULTS: Those receiving the high soya diet showed significant improvements in short-term (immediate recall of prose and 4-s delayed matching to sample of patterns) and long-term memory (picture recall after 20 min) and in mental flexibility (rule shifting and reversal). These improvements were found in males and females. In a letter fluency test and in a test of planning (Stockings of Cambridge), the high soya diet improved performance only in females. There was no effect of diet on tests of attention or in a category generation task. Those on the high soya diet rated themselves as more restrained and, after the tests of memory and attention, they became less tense than did those on the control diet. CONCLUSIONS: Significant cognitive improvements can arise from a relatively brief dietary intervention, and the improvements from a high soya diet are not restricted to women or to verbal tasks.     

Double-blind,placebo-controlled study comparing effects of zopiclone and temazepam on cognitive functioning of insomniacs

The purpose of this study was to compare the cognitive effect of two medications frequently prescribed to patients suffering from insomnia. Using a double-blind design, we evaluated three parallel groups of 20 insomniac patients treated over a period of 3 weeks with zopiclone, temazepam and placebo, respectively. Our hypothesis was that the impact of zopiclone 7.5 mg/day on cognitive functioning would be minimal 12 h after administration and that temazepam 30 mg/day would affect explicit memory, as is the case with other benzodiazepines. Patients were assessed at baseline following a 1-week, single-blind placebo-intake period, and again at the end of each of the 3 weeks of the comparative phase. Then, in order to estimate the severity and duration of potential rebound insomnia, patients were again assessed following another 1-week, single-blind placebo-washout period at the end of the 3 weeks of treatment. The overall duration of the study for each patient was thus 5 weeks. The instruments of measure used were the Hamilton scale for anxiety, daily self-rating questionnaire for assessment of sleep onset, duration and quality, and two large batteries of psychometric tests. The first of these batteries assessed memory and included span tests for short-term memory, cued recall tasks for long-term explicit memory, and a word-completion task for implicit memory; the second measured attention and concentration through the assessment of alertness, sustained attention and divided attention. The sleep and anxiety results obtained confirm the findings of previous research. Zopiclone and temazepam possess a clinically significant hypnotic activity, with no rebound insomnia or anxiety, during the week of drug withdrawal. The results indicate that the two hypnotic drugs studied have little impact on cognitive functioning. We can therefore conclude that at the doses administered over the 3 weeks, the two hypnotic drugs in question are relatively safe and efficacious in the treatment of insomnia and enable patients to enjoy a good quality of life. Copyright © 1999 John Wiley & Sons, Ltd.     

Amitriptyline,clovoxamine and cognitive function: a placebo-controlled comparison in depressed outpatients

No longer prescribed only for vegetative signs of depression, tricyclic antidepressants also lessen depressive cognitive distortions. Less clear is whether they ameliorate depressed patients' other cognitive deficits in memory, information processing speed, and psychomotor performance. We tested the alternative hypothesis that amitriptyline, because of its anticholinergic and sedative properties, would exacerbate depressed patients' cognitive disturbances. Depressed outpatients received double-blind placebo (n=15), amitriptyline (n=10), or clovoxamine fumarate (n=10), a serotonin reuptake inhibitor relatively lacking in anticholinergic properties. Depression, memory, and psychomotor performance were assessed at baseline and after 7 and 28 days of drug treatment. Depression was alleviated after all treatments, including placebo. Only amitriptyline impaired performance on tests of memory, producing a significant decrement, relative to placebo, after 4 weeks of treatment. None of the treatments adversely affected performance on psychomotor tasks. These findings add to the evidence that antidepressant drugs with high anticholinergic activity can impair memory, despite alleviation of depression.     

Mechanism of improvement of spatial cognition with dietary docosahexaenoic acid

We estimated the effects of dietary administration of docosahexaenoic acid (DHA, 22:6n-3) on rat spatial cognition using young male Wistar rats. Chronic administration of DHA to rats increased the hippocampal levels of DHA. Six weeks after the start of the administration, the rats were for 5 weeks trained to acquire a reward at the end of each of 4 arms of an 8-arm radial maze. The retention test interposed with a delayed task (20-min interval after the first 2 free choices) was then given to each rat to determine spatial working memory retention. On completion of the test, the Fos expression in the hippocampus was examined immunohistochemically. DHA administration reduced the number of working memory errors after the 20-min interval in the retention test. The number of Fos-positive neurons in the CA1 hippocampus demonstrated a statistically significant negative correlation with the number of working memory errors, suggesting that the DHA-induced improvement in spatial cognition is associated with increased Fos expression in the CA1 hippocampus.     

Ladostigil prevents gliosis, oxidative-nitrative stress and memory deficits induced by intracerebroventricular injection of streptozotocin in rats

Glial activation and oxidative-nitrative stress occur at an early stage in Alzheimer's disease (AD). In a rat model of AD, deficits in cerebral glucose utilization and memory were seen 3-4 weeks after intracerebroventricular (icv) injection of streptozotocin (STZ). This study examined whether icv STZ induced glial activation and oxidative-nitrative stress preceded the memory deficits and whether they could be prevented by ladostigil a novel drug, a cholinesterase and monoamine oxidase inhibitor with neuroprotective activity. One week after STZ injection activated microglia and astrocytes were seen in the cortex, around the cannula penetration area, in the hippocampal CA1 region, corpus callosum, medial and lateral septum. The activated astrocytes showed a significant increase in nitrotyrosine immunoreactivity, a measure of oxidative-nitrative stress. Only 3 weeks later were deficits in episodic (object recognition test) and spatial memory (place recognition) seen in STZ-injected rats. Daily oral administrations of ladostigil (1mg/kg) for 1 week, before and after STZ prevented the glial changes, increase in nitrotyrosine immunoreactivity and memory deficits. Taken together the data support the role of glial activation and oxidative-nitrative stress in discrete brain areas in the aetiology of memory deficits and indicate a potential mechanism for their prevention by drug treatment.     

文拉法辛与舍曲林对抑郁症患者认知功能的影响比较

目的 探讨文拉法辛对抑郁症患者认知功能的影响.方法 将未用过抗抑郁药物和其他抗精神病药物的84例患者随机分为文拉法辛组(A组)和舍曲林组(B组),分别在治疗前和治疗12周后使用数字广度测验和空间工作记忆测验评定工作记忆改善情况,使用图案再认测验、配对学习测验和延迟匹配测验评定视觉记忆改善情况,使用反应时测验和斯特鲁普色词测验评定工作记忆改善情况,使用汉密尔顿抑郁量表(HAMD-17)评定疗效.结果 两组患者的空间工作记忆测验、图案再认测验、配对学习测验和斯特鲁普色词测验成绩在治疗后显著提高(P<0.05或P<0.01),A组的延迟匹配测验成绩显著高于B组(P<0.05),治疗时间因素和药物分组因素在数字广度测验和配对学习测验成绩上的交互作用显著(P<0.05或P<0.01).结论 文拉法辛和舍曲林对抑郁症患者工作记忆、视觉记忆和心理加工速度方面的认知功能均有一定改善作用,文拉法辛改善工作记忆和视觉记忆的作用比舍曲林更明显.     

银杏叶提取物对缓激肽诱导的大鼠记忆能力减退的改善作用

目的观察银杏叶提取物(GBE)对缓激肽诱导的大鼠记忆能力减退的改善作用,并探索其作用机制。方法大鼠经Morris水迷宫训练合格后,分别灌胃给予GBE(40,80和160mg.kg-1,每日1次)3周,于给药1周时海马内注射20mmol.L-1缓激肽5μL,给药结束后用Morris水迷宫检测大鼠的空间记忆能力,RT-PCR法测定海马半胱氨酸天冬氨酸蛋白酶(caspase)3及caspase8mRNA的表达。结果海马内注射缓激肽后,大鼠在水迷宫中的逃避潜伏期和寻台搜索距离明显延长,且海马caspase3和caspase8mRNA表达增加;GBE对缓激肽诱导的空间记忆能力减退有改善作用,且降低海马caspase3及caspase8mRNA表达。结论GBE可改善缓激肽诱导的大鼠记忆能力减退,其机制可能与降低海马caspase3和caspase8mRNA表达有关。