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

1)为了评价促性腺激素药物的治疗潜力，最理想的是建立相关的动物学习和记忆测试方法。延迟匹配样本法(DMSP)是测定短时记忆的实验方法之一。建立了两种研究大鼠工作记忆的新方法，分别用DMSP在三级操纵器和三级跑道装置上进行，在三级跑道任务中，东莨菪碱(0.56 mg/kg，ip.)和AF64A(双侧向背侧海马区注射2.5nmol)显著增加了错误(动物按下错误的面板门的次数)和潜伏期(动物摄取目标盒盘子上的食物颗粒所需的时间)。在三级操作任务中，东莨菪碱(0.32 mg/kg，i.p.)减少了测试试验中的增援人数，而不减少训练试验中的增援人数。这些结果提示胆碱能系统功能障碍导致…功能紊乱。在两个任务中，更多的记忆(短期记忆)。另一方面，嗅球切除和背侧海马区损伤都损害了这两个任务中的工作记忆，但乳头体的损伤在操作员任务中没有。为了阐明THA和蛋氨酸的区别刺激特性，胆碱酯酶抑制剂四氢氨基吖啶(THA)和胺基、胆碱能激动剂WEB 1881FU和米纳平以及甲基供体S-腺苷-L-蛋氨酸改善了东莨菪碱或三组跑道任务中缺血造成的工作记忆损害。对两组不同的大鼠进行训练，以辨别两种药物中的任一胺(10 mg/kg，i.p)。或THA(1.8 mg/kg ip)。在标准的两级食品强化程序(FR10)上使用生理盐水。胆碱酯酶抑制剂是胺基吡啶。在THA和毒扁豆碱训练的大鼠中，THA和毒扁豆碱均产生剂量依赖的药物适当反应。槟榔碱完全替代了胺类兴奋剂，部分替代了THA刺激剂。这两种刺激物均可被东莨菪碱所阻断。另一方面，利尿胺在两种训练的大鼠中也产生完全的药物相关反应，金刚烷胺在胺和THA训练的大鼠中分别产生完全的药物相关反应和60%的药物相关反应，但氟哌啶醇、SCH 23390和舒必利均不能拮抗这两种辨别刺激。此外，非竞争性NMDA拮抗剂苯环利定和右旋糖胺，以及促性药物WEB 1881FU和霍普坦酸钙对酰胺和THA刺激表现出部分泛化。这些结果表明，胆碱能易化对胺基吡啶和THA的辨别刺激具有重要作用。较少

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