琥珀酰CCK—7对小鼠记忆的影响

琥珀酰ＣＣＫ－７是对ＣＣＫ－８进行分子改构后获得的一种新药，本实验以一次被动回避反应模型观察比较了这种改构物与ＣＣＫ－８对小鼠记忆巩固过程的影响，同时探讨了ｓｕｃ－ＣＣＫ－７影响记忆过程的剂量－效应关系以及时相－效应关系。结果表明：（１）ｓｕｃ－ＣＣＫ－７促进记忆的有效剂量为１００－２００μｇ／ｋｇ，小于１００μｇ／ｋｇ无明显效应。（２）ｓｕｃ－ＣＣＫ－７增强小鼠记忆的效应在电击后４８ｈ最明显，７

EFFECT OF SUC-CCK-7 ON THE MEMORY OF MICE

Cholecystokinin (CCK) exists extensively in the nervous system and belongs to brain-gastrointestinal peptide. The highly effective fragment of CCK molecule isthe C-terminal eight amino acids. The brain contains mainly CCK-8. In recent years, theeffects of CCK on brain function have been investigated and structure-activity studies reveal that CCK-8 improves animal memory consolidation and CCK-4 has an effect opposite to that of CCK-8, i.e. it leads to an impairment of memory or amnesia. Succinylcholecystokinin heptapeptide (sue=CCK--7) is derived from cholecystokinin octapeptide(CCK--8) by the change of N--terminal aspartate. It has some advantages, such as goodwater--solubility and availability and convenienCe foe the syntheSis. Therefore, it is important to observe the influence of Sue--CCK--7 on memory processes and to compare it withCCK--8.'so that it is convenient to find out the correlation of molecular structure--activityand to seek for a useful'substitute of CCK--8. In this experiment, the effects of sue--CCK--7and CCK--8 on memory consolidation processes of mice were observed by thee passiveavoidance paradigm. In the meantime, the dose--response relationship and time--responserelationship for the behavioral'effects of sue--CCK--7 were also studied. The main results ofthe experiment are as follows: l.The effeCtive dose of facilitating memory of sue--CCK--7]was 100--200pg. kg'. When its dose w4s less than 100pg. kg', sue--CCK'--7 had no significant effect on the memory of mice. 2. The facilitation of sue--CCK,7 on the memorywere significant al 48hr after a aversive experience. These effects decreased to the controllevel at 72hr follpwing electric foot--shocks. 3. The facilitating effects.of sue--CCK-7 on thememory.weth antagonized by proglumide. 4. Sue--CCK--7 had an effwt similar to that ofCCK--8 in facilitation of retention. These findings indicate that the asparticacid of molecular N--terminal of CCK--8 had no significant effect on memory consolidation.