The Behavioral and Pharmacological Study on Experimental Amnesia By using a New Method For Measuring Short-term Memory.

使用测量短期记忆的新方法对实验性遗忘症进行行为和药理学研究。

• 批准号: 01570108
• 负责人: YAMAMOTO Tsuneyuki
• 金额: $ 1.41万
• 依托单位: Kyusyu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570108/
• 关键词: 3-lever operant task; 3-panel runway task; brain lesion; Working memory; impairment of memory; drug discrimination; tetrahydroaminoacridine; delayed matching-to-sample procedure; 短期記憶; 学習・記憶; コリンエステラ-ゼ阻害薬; runway 学習; operant 学習; 作業記憶; 脳局所破壊

1) For evaluating the therapeutic potential of nootropic drugs, it is most desirable to establish relevant methods for measuring "learning and memory" in animals. The Delayed Matching-to-Sample Procedure (DMSP) is one of the experimental methods for determining short-term memory. I established two new methods for the study of working memory in the rat, using the DMSP in 3-lever operant apparatus and 3- panel runway apparatus.In the 3-panel runway task, scopolamine (0.56mg/kg i. p.) and AF 64A (2.5nmol bilaterally injected into the dorsal hippocampus) significantly increased errors (the number of times an animal pushed an incorrect panel-gate) and latency (the time required for the animal to take food-pellets on the plate of the goal box). In the 3-lever operant task, scopolamine (0.32mg/kg i. p.) decreased the number of reinforces in test trials without decreasing that in training trials. These findings suggest that dysfunction of cholinergic system lead to disturbances of the working … More memory (short-term memory) in both tasks.On the other hand, olfactory bulbectomy and dorsal hippocampus lesions impaired the working memory in both tasks, but lesions of the mammillary body did not in the operant task.The impairment of working memory produced by scopolamine or ischemia in a 3-panel runway task was ameliorated by cholinesterase inhibitors Tetra-Hydro-Aminoacridine (THA) and amiridin, cholinergic activators WEB 1881 FU and minaprine, and a methyl donor S-adenosyl-L-methionine.2) In order to clarify the discriminative stimulus properties of THA and amiridin. Two different groups of rats were trained to discriminate either amiridin (10mg/kg i. p.) or THA (1.8mg/kg i. p.) from saline on a standard two-lever Food-Reinforced procedure (FR10). Cholinesterase inhibitors amiridin. THA and physostigmine produced a dose-dependent drug-appropriate responding both in amiridin and in THA trained rats. Arecoline substituted completely for amiridin stimuli and partially for THA stimuli. Both the amiridin and THA stimuli were blocked by scopolamine. On the other hand, lisuride alsoproduced full drug-appropriate responding in both trained rats, and amantadine produced full and 60% drug-appropriate responding in the amiridin and THA trained rats, respectively.However, haloperidol, SCH 23390 and sulpiride failed to antagonize both discriminative stimuli. Further, non-competitive NMDA antagonists phencyclidine and dextrophan, and nootropic drugs WEB 1881 FU and calcium hopantenate showed partial generalization to the amiridin and THA stimuli. These results indicate that cholinergic facilitation is important for the discriminative stimuli of amiridin and THA. Less

1）为了评估促智药物的治疗潜力，最需要建立测量动物“学习和记忆”的相关方法。延迟匹配样本程序（DMSP）是确定短期记忆的实验方法之一。我建立了两种研究大鼠工作记忆的新方法，分别在 3 杆操作装置和 3 面板跑道装置中使用 DMSP。 在 3 面板跑道任务中，东莨菪碱（腹腔注射 0.56 毫克/千克）和 AF 64A（2.5 纳摩尔双侧注射到背侧海马）显着增加了错误（动物推动错误的次数）。 面板门）和潜伏期（动物在球门盒的板上获取食物颗粒所需的时间）。在三杠杆操作任务中，东莨菪碱（0.32mg/kg i. p.）减少了测试试验中的强化数量，而没有减少训练试验中的强化数量。这些发现表明，胆碱能系统功能障碍会导致这两项任务中的工作记忆（短期记忆）紊乱。另一方面，嗅球切除术和背侧海马病变会损害这两项任务中的工作记忆，但乳头体的病变不会影响操作任务中的工作记忆。东莨菪碱或缺血产生的工作记忆损害在三面板中 胆碱酯酶抑制剂四氢氨基吖啶（THA）和amiridin、胆碱能激活剂WEB 1881 FU和minaprine以及甲基供体S-腺苷-L-蛋氨酸改善了跑道任务。2）为了阐明THA和amiridin的辨别刺激特性。两组不同的大鼠经过训练，通过标准双杆食物强化程序 (FR10) 区分阿米里丁 (10mg/kg i. p.) 或 THA (1.8mg/kg i. p.) 与盐水。胆碱酯酶抑制剂阿米里丁。 THA 和毒扁豆碱在amiridin 和THA 训练的大鼠中产生剂量依赖性药物适当反应。槟榔碱完全替代amiridin刺激并部分替代THA刺激。阿米里丁和 THA 刺激均被东莨菪碱阻断。另一方面，麦角乙脲也在两只经过训练的大鼠中产生了完全的药物适当反应，而金刚烷胺分别在阿米里丁和THA训练的大鼠中产生了完全和60%的药物适当反应。然而，氟哌啶醇、SCH 23390和舒必利未能拮抗两种辨别刺激。此外，非竞争性 NMDA 拮抗剂苯环己哌啶和右旋凡，以及促智药物 WEB 1881 FU 和藿潘酸钙显示出对amiridin 和 THA 刺激的部分泛化。这些结果表明胆碱能促进对于amiridin 和THA 的辨别刺激很重要。较少的

项目成果

T.Yamamoto,: "Effects of nootropic drugs on experimentally induced amnesia of rats using the three-panel runway task.In:Alzheimer's and Parkingson's diseases." Plenum Press,

T.Yamamoto：“使用三组跑道任务，促智药物对实验性诱发的大鼠失忆症的影响。见：阿尔茨海默病和帕金森病。”

M.Ohno et al.: "Blockade of 5ーHT_2 receptors protects against impairment of working memory following transient forebrain ischemia in the rat" Neurosci.Lett.(1991)

M.Ohno 等人：“阻断 5-HT_2 受体可防止大鼠短暂前脑缺血后工作记忆受损” Neurosci.Lett.(1991)

T.Yamamoto: "Minaprine improves impairment of working memory induced by scopolamine and cerebral ischemia in rats." Psychopharmacology. 100. 316-322 (1990)

T.Yamamoto：“米那普林改善了东莨菪碱引起的大鼠工作记忆损伤和脑缺血。”

T.Yamamoto et al.(edited by T.Nagatsu et al.): "Effects of Nootropic drugs on experimentally induced amnesia of rats using the threeーpanel runway task.In:Alzheimer´s and Parkinson´s Diseases(vol.2)" Plenum Press (New York), 615 (1991)

T.Yamamoto 等人（由 T.Nagatsu 等人编辑）：“促智药物对使用三面板跑道任务实验诱导的大鼠遗忘症的影响。见：阿尔茨海默病和帕金森病（第 2 卷） ）”全会出版社（纽约），615（1991）

T.Yamamoto: "Inhibition of mouse-killing behavior by S-adenosyl-L-methionine inmidbrain raphe-lesioned and olfactory-bulbectomized rats." Pharmacol.Biochem.Behav.4(2). 395-398 (1989)

T.Yamamoto：“S-腺苷-L-甲硫氨酸在中脑中缝损伤和嗅球切除的大鼠中抑制小鼠杀戮行为。”