Aricioglu Feyza, Paul Ian A, Regunathan Soundar
Marmara University, Faculty of Pharmacy, Department of Pharmacology, Istanbul, Turkey.
Neurosci Lett. 2004 Jan 9;354(2):153-7. doi: 10.1016/j.neulet.2003.10.010.
Agmatine inhibits morphine tolerance/dependence and potentiates morphine analgesia. This study was designed to investigate whether neuronal nitric oxide mediates the actions of agmatine in morphine dependence by using mice lacking a functional form of this enzyme. Mice received agmatine just after the morphine pellet implantation for 3 days twice daily or single injection 30 min before naloxone. In both genotypes treated for 3 days with morphine pellets, naloxone administration precipitated clear signs of withdrawal. Both acute and chronic administration of agmatine reduced withdrawal signs in wild type mice and reduced only peripheral signs of morphine dependence in neuronal nitric oxide synthase knockout mice. Withdrawal signs, that are related to central nervous system activity were not affected. These findings indicate that neuronal nitric oxide synthase partly mediates the effects of agmatine in morphine physical dependence.
胍丁胺可抑制吗啡耐受性/依赖性，并增强吗啡镇痛作用。本研究旨在通过使用缺乏该酶功能形式的小鼠，研究神经元型一氧化氮是否介导胍丁胺在吗啡依赖性中的作用。小鼠在植入吗啡丸剂后立即接受胍丁胺，每日两次，持续3天，或在纳洛酮前30分钟单次注射。在两种基因型中，用吗啡丸剂治疗3天后，给予纳洛酮可引发明显的戒断症状。急性和慢性给予胍丁胺均可减轻野生型小鼠的戒断症状，而在神经元型一氧化氮合酶基因敲除小鼠中，仅减轻吗啡依赖性的外周症状。与中枢神经系统活动相关的戒断症状未受影响。这些发现表明，神经元型一氧化氮合酶部分介导了胍丁胺在吗啡身体依赖性中的作用。
