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.

为了评估促性腺激素药物的治疗潜力，最理想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，我们设计了两种新的测量短期记忆的装置：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大鼠可以向球门方向通过面板门，但不能通过起跑箱。大鼠在目标箱中给予100 mg食物颗粒作为阳性强化。每天进行一次训练。一次会议包括六次试验。每只大鼠正确的门位置顺序每天都在变化，但不是在一次会议中。2)四杆操纵器配备四杆和一个食物托盘。雄性Wistar大鼠每天训练15次(FR 3；食物颗粒为阳性强化)，延迟30秒。一个实验由训练实验和测试实验组成，每个实验持续30秒，Ru…的这两个学习在训练20次和30次后，分别建立了更多的Nway任务和操作任务，东莨菪碱HBr以剂量依赖的方式增加错误次数。海马区注射乙胆碱氮丙啶离子(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作用，这些过程将有助于研究大鼠的短期记忆。另一方面，药物辨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灵敏的技术。在大鼠双水平操作任务(FR 10)下，还建立了促性腺激素药物厚朴酸钙(500 mg/kg)对生理盐水的分辨作用。毒扁豆碱、氨基氧乙酸和Musiol被部分推广到触角刺激。阿托品可部分阻断对触角神经元的刺激。因此，我们发现，跳跃式辨别刺激部分是由于胆碱能和GABA能系统的激活所致。较少

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