Nanri M, Kaneto H
Nihon Yakurigaku Zasshi. 1987 Jun;89(6):323-9. doi: 10.1254/fpj.89.323.
Based on the results of a previous report that prolyl endopeptidase (PPCE) inhibitors facilitated the acquisition of active avoidance response and retarded the extinction of the response, further studies were made on the effect of PPCE inhibitors on learning and the memory process. Using mice, tests were performed both in the light-dark discrimination Y-maze task and the lever-press task of the water reinforcement schedule, and mice were also tested in the acquisition and retention of one-trial "step-through" passive avoidance task. The effect of PPCE inhibitors were investigated both in control and electroconvulsive shock- or scopolamine-induced amnesic animals. Z-Pro-p, the most potent inhibitor among 5 compounds tested in this study, and arginine vasopressin (AVP) facilitated the learning process and retarded the extinction of the acquired response in all tests. Suc-Pro-p was also effective in the Y-maze and passive avoidance test. Thus, the effect of the test compounds were parallel with their in vitro activities as PPCE inhibitor. These results suggest that the anti-amnesic effect of PPCE inhibitors is partially attributable to their effect on the breakdown of the biologically active peptides which are involved in the memory process, such as AVP, in the brain.
基于先前一份报告的结果，即脯氨酰内肽酶（PPCE）抑制剂促进了主动回避反应的习得并延缓了该反应的消退，因此对PPCE抑制剂对学习和记忆过程的影响进行了进一步研究。使用小鼠，在明暗辨别Y迷宫任务和水强化程序的杠杆按压任务中进行测试，并且还对小鼠进行了单次“穿梭”被动回避任务的习得和保持测试。在对照动物以及电休克或东莨菪碱诱导的记忆缺失动物中研究了PPCE抑制剂的作用。Z-Pro-p是本研究中测试的5种化合物中最有效的抑制剂，精氨酸加压素（AVP）在所有测试中均促进了学习过程并延缓了习得反应的消退。Suc-Pro-p在Y迷宫和被动回避测试中也有效。因此，测试化合物的作用与其作为PPCE抑制剂的体外活性是平行的。这些结果表明，PPCE抑制剂的抗记忆缺失作用部分归因于它们对大脑中参与记忆过程的生物活性肽（如AVP）分解的影响。
