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.

为了评估益智药物的治疗潜力，最需要的是建立相关的方法来测量动物的“学习和记忆”。在这项研究中，我们设计了两个新的测量短期记忆的仪器。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鼠可以通过球门方向的板门，但不能通过出发箱方向的板门。在球门内给予大鼠100 mg食物颗粒作为正强化。训练每天进行一次。一次会议包含六次试验。每只大鼠的正确门位置顺序每天改变，但不是在一个疗程中改变。2)四杆操作装置配有四杆和一个食物托盘。雄性Wistar大鼠每天连续训练15次（FR 3；食物颗粒作为正强化），间隔30秒。一个试验由训练和测试两部分组成，每部分训练时间为30秒，在训练20次和30次后分别建立更多的学习任务和操作性任务。东莨菪碱HBr以剂量依赖的方式增加了误差的数量。海马内乙胆碱偶氮离子（AF64A）也增加了错误次数。这些结果表明，胆碱能系统在这些任务的工作记忆中起着重要的作用，这些过程对研究大鼠的短期记忆有一定的帮助。另一方面，药物鉴别刺激的使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。在两级操作任务（fr10）下，还建立了一种促智药——麻藤酸钙（500 mg/kg）与生理盐水的区别。毒豆碱、氨基氧乙酸和麝香酚部分被推广到麻藤酸刺激。阿托品部分阻断hoptenate刺激。因此，我们发现麻酸鉴别刺激是由于激活了胆碱能和gaba能系统的一部分。少

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