Jalkanen Aaro J, Puttonen Katja A, Venäläinen Jarkko I, Sinervä Veijo, Mannila Anne, Ruotsalainen Sirja, Jarho Elina M, Wallén Erik A A, Männistö Pekka T
Department of Pharmacology and Toxicology, University of Kuopio, Kuopio, Finland.
Basic Clin Pharmacol Toxicol. 2007 Feb;100(2):132-8. doi: 10.1111/j.1742-7843.2006.00021.x.
The effects of a novel prolyl oligopeptidase (POP) inhibitor KYP-2047 on spatial memory of young (3-month-old) and old (8- to 9-month-old) scopolamine-treated rats (0.4 mg/kg intraperitoneally) was investigated in the Morris water maze. In addition, the concentrations of promnesic neuropeptide substrates of POP, substance P and neurotensin in various brain areas after acute and chronic POP inhibition were measured in young rats. In addition, inositol-1,4,5-trisphosphate (IP(3)) levels were assayed in rat cortex and hippocampus after effective 2.5-day POP inhibition. KYP-2047 (1 or 5 mg/kg 30 min. before daily testing) dose-dependently improved the escape performance (i.e. latency to find the hidden platform and swimming path length) of the young but not the old rats in the water maze. POP inhibition had no consistent effect on substance P levels in cortex, hippocampus or hypothalamus, and only a modest increase in neurotensin concentration was observed in the hypothalamus after a single dose of KYP-2047. Moreover, IP(3) concentrations remained unaffected in cortex and hippocampus after POP inhibition. In conclusion, the behavioural data support the earlier findings of the promnesic action of POP inhibitors, but the mechanism of the memory-enhancing action remains unclear.
在莫里斯水迷宫中研究了新型脯氨酰寡肽酶（POP）抑制剂KYP - 2047对经东莨菪碱（0.4mg/kg腹腔注射）处理的年轻（3个月大）和老年（8至9个月大）大鼠空间记忆的影响。此外，还测量了年轻大鼠急性和慢性抑制POP后，各脑区中POP的促记忆神经肽底物P物质和神经降压素的浓度。另外，在有效抑制POP 2.5天后，检测大鼠皮层和海马中的肌醇 - 1,4,5 - 三磷酸（IP(3)）水平。KYP - 2047（每日测试前30分钟给予1或5mg/kg）剂量依赖性地改善了年轻大鼠在水迷宫中的逃避表现（即找到隐藏平台的潜伏期和游泳路径长度），但对老年大鼠没有作用。抑制POP对皮层、海马或下丘脑的P物质水平没有一致的影响，单次给予KYP - 2047后，仅观察到下丘脑神经降压素浓度有适度增加。此外，抑制POP后，皮层和海马中的IP(3)浓度未受影响。总之，行为学数据支持了早期关于POP抑制剂促记忆作用的研究结果，但记忆增强作用的机制仍不清楚。
