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.

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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