Dynorphin A (2-13) improves mecamylamine-induced learning impairment accompanied by reversal of reductions in acetylcholine release in rats
Dynorphin A (2-13) improves mecamylamine-induced learning impairment accompanied by reversal of reductions in acetylcholine release in rats
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DOI：
10.1016/j.npep.2005.10.003
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发表时间：
2006-02-01
期刊：
影响因子：
2.9
通讯作者：
Watanabe, E
中科院分区：
文献类型：
--
作者：
Hiramatsu, M;Watanabe, E
越来越多的证据表明，内源性阿片肽强啡肽 A (1 -17) 和合成强啡肽 A (1-13) 不仅与阿片受体相互作用，而且还与尚未充分表征的非阿片结合位点相互作用。强啡肽 A (1-13) 不仅通过 K-阿片受体介导的机制，而且还通过“非阿片类药物”机制改善学习和记忆障碍。在本研究中，使用逐步型被动回避任务研究了去酪氨酸强啡肽 A (2-13) 作为强啡肽 A 的非阿片类代谢物和强啡肽 A (1-13) 油美加明诱导的大鼠学习障碍的影响。此外，使用体内微透析检查海马乙酰胆碱释放。在采集试验前 30 分钟给予美加明可显着缩短逐步潜伏期。不仅强啡肽 A (1-13) 而且强啡肽 A (2-13) 都能减轻美加明引起的学习障碍。强啡肽 A (2-13) 的作用不会被去甲二托菲明 (nor-BNI)（一种选择性 K-阿片受体拮抗剂）预处理所阻断。强啡肽 A (2-13) 完全消除了美加明引起的细胞外乙酰胆碱浓度的降低，并且这种作用不被 Nor-BNI 阻断。与我们之前的发现结合起来，目前的结果可能表明，强啡肽 A (2-13) 可以改善“非阿片类药物”机制中的学习和/或记忆障碍，而强啡肽 A (1-13) 不仅可以通过 (K)-阿片类药物受体介导的机制，还可以通过调节细胞外乙酰胆碱的释放，通过“非阿片类药物”机制来改善学习障碍。 (c) 2005 Elsevier Ltd. 保留所有权利。
Accumulating evidence indicates that the endogenous opioid peptides dynorphin A (1 -17) and synthetic dynorphin A (1-13) interact not only with opioid receptors but also with as yet poorly characterized non-opioid binding sites. Dynorphin A (1-13) improved impairments of learning and memory via not only K-Opioid receptor-mediated, but also 'non-opioid' mechanisms. In the present study, the effects of des-tyrosine dynorphin A (2-13) as a non-opioid metabolite of dynorphin A, and dynorphin A (1-13) oil mecamylamine-induced impairment of the acquisition of learning in rats were investigated using a step-through type passive avoidance task. Further, hippocampal acetylcholine release was examined using in vivo microdialysis. Mecamylamine sianificantly shortened the step-through latency when given 30 min before the acquisition trial. Not only dynorphin A (1-13) but also dynorphin A (2-13) attenuated the mecamylamine-induced impairment of the acquisition of learning. The effect of dynorphin A (2-13) was not blocked by pre-treatment with nor-binaltorphimine (nor-BNI), a selective K-opioid receptor antagonist. Dynorphin A (2-13) completely abolished the decrease in the extracellular acetylcholine concentration induced by mecamylamine and this effect was not blocked by nor-BNI. Taken together with our previous findings, the present results may indicate that dynorphin A (2-13) improves impairment of learning and/or memory in 'non-opioid' mechanisms and dynorphin A (1-13) ameliorates impairment of the acquisition of learning via not only (K)-Opioid receptor-mediated mechanisms but also 'non-opioid' mechanisms, by regulating the release of extracellular acetylcholine. (c) 2005 Elsevier Ltd. All rights reserved.