The elucidation of the mechanism of Anti-dimentia effects of nootropic drugs and The establishment of pre-clinical screening method for evaluating its therapeutic potential.

阐明促智药物抗痴呆作用的机制并建立评估其治疗潜力的临床前筛选方法。

• 批准号: 60570094
• 负责人: YAMAMOTO Tsuneyuki
• 金额: $ 0.96万
• 依托单位: Kyushu 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: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60570094/
• 关键词: working memory; operant task; runway task; drug discrimination; nootropic drug; Ca hopantenate; scopolamine; 遅延見合わせ課題

For evaluating the therapeutic potential of nootropic drugs, it is most desirable to establish relevant methods for measuring "learning and memory" in animals. In this study, we designed two new apparatus to measure short-term memory.1) The runway apparatus is composed of four consecutive choice points; each choice point consists of three panel gates. Male Wistar rat can pass through the panel gate in the direction of goal box but not start box. Rats were given 100 mg food pellets in goal box as positive reinforcement. Training was performed one session per day. One session contains six trials. The sequence of correct gate position in each rat was changed everyday but not in a session.2) 4-lever operant apparatus is fitted with 4-levers and one food-tray. Male Wistar rats are trained for 15 consecutive trials per day (FR 3; food-pellet as positive reinforcement), with a 30 sec delay interval. One trial is composed of the training and test trial, each for 30 sec.These two learning of ru … More nway task and operant task were established after 20 and 30 training sessions, respectively.Scopolamine HBr increased the number of errors in a dose dependent manner. Intra-hippocampal ethylcholine aziridinium ion (AF64A) also increased the number of errors.These results suggest that cholinergic system has an important role in the working memory of these tasks and these procedure would be useful for studying shortterm memory in rats.On the other hand, the use of drug discriminative stimuli is expected to provided a sensitive technique for elucidating the mechanism of action of psychoactive drugs. A nootropic drug, calcium hopantenate (500 mg/kg) vs saline discrimination was also established in rats under the 2-lever operant task (FR 10). Physostigmine, amino-oxyacetic acid and musimol were partially generalized to hopantenate stimuli. Hopantenate stimulus was partially blocked by atropine. Therefore, it is found that hopantenate discriminative stimulus is due to activation of cholinergic and GABAergic system in a part. Less

为了评价促智药物的治疗潜力，最需要建立用于测量动物“学习和记忆”的相关方法。本研究设计了两种测量短时记忆的新装置：1）跑道装置由四个连续的选择点组成，每个选择点由三个面板门组成。雄性Wistar大鼠可以通过球门方向的板门，但不能通过出发方向的板门。在目标箱中给予大鼠100 mg食物颗粒作为正强化。每天进行一次培训。一次开庭包括六次审判。每只大鼠的正确门位置的顺序每天改变，但不是在一个会话中。2）4杠杆操作装置配有4个杠杆和一个食物托盘。每天训练雄性Wistar大鼠15次连续试验（FR 3;食物颗粒作为正强化），延迟间隔为30秒。一次试验由训练和测试试验组成，每次30秒。 ...更多信息 分别在20次和30次训练后建立了正向任务和操作任务，东莨菪碱使错误数呈剂量依赖性增加。海马内注射乙基胆碱氮丙啶离子（AF 64 A）也能增加错误次数，提示胆碱能系统在这些任务的工作记忆中起重要作用，这一过程对研究大鼠短时记忆有重要意义，而药物辨别性刺激的应用有望为阐明精神活性药物的作用机制提供一种敏感的技术。还在大鼠的2级操作任务（FR 10）下建立了促智药乌帕腾酸钙（500 mg/kg）与盐水辨别。毒扁豆碱，氨基氧乙酸和musimol部分推广到hopantenate刺激。阿托品可部分阻断霍潘顿酸刺激。因此，我们认为，霍潘顿酸类辨别性刺激在一定程度上是由于胆碱能和GABA能系统的激活。少

项目成果

Tsuneyuki Ymamoto: Physiol.and Behav.

山本常之：生理和行为。

Tsuneyuki Yamamoto: "Discriminotive stimulus properties of Ca-hopantenate in rats" Pharmac. Biochem. Behav.

Tsuneyuki Yamamoto：“Ca-hopantenate 对大鼠的辨别刺激特性”Pharmac。

Yoshiaki Furuya: "A new method for measuring working memory in rats by using a Hill's runway apparatus" Jpn. J. Psychopharmacol.7. 223-224 (1987)

Yoshiaki Furuya：“使用希尔跑道仪测量大鼠工作记忆的新方法”Jpn。

Tsuneyuki Yamamoto: "A new method for measuring working memory in rats by using a 4-lever operant apparatus" Physiol. and Behav.

Tsuneyuki Yamamoto：“一种使用 4 杆操作装置测量大鼠工作记忆的新方法”Physiol。

Tsuneyuki Yamamoto: Japan J.Pharmacol.39. )29 (S (1985)

Tsuneyuki Yamamoto：日本 J.Pharmacol.39。