The effect of L-NAME and L-arginine on impairment of memory formation and state-dependent learning induced by morphine in mice
The effect of L-NAME and L-arginine on impairment of memory formation and state-dependent learning induced by morphine in mice
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DOI：
10.1007/s00213-002-1377-7
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发表时间：
2003-05-01
影响因子：
3.4
通讯作者：
Zarrindast, MR
中科院分区：
文献类型：
--
作者：
Khavandgar, S;Homayoun, H;Zarrindast, MR
基本原理：吗啡和一氧化氮（NO）在不同的神经过程中具有重要的功能相互作用，并且都调节学习和记忆，尽管它们在认知表现中的相互作用尚未阐明。目的：研究一氧化氮合酶（NOS）抑制剂N-硝基-L-精氨酸甲酯（N-G-nitro-L-arginine methyl ester，L-NAME）和NOS底物L-精氨酸（L-arginine）对吗啡诱导的记忆形成障碍和被动回避任务的状态依赖性提取的影响。研究方法：所有药物均经腹膜内给药，并采用一次试验逐步下降模式评估成年雄性NMRI小鼠的记忆力。在训练前30分钟给予吗啡以诱导记忆形成的损害，在测试前30分钟给予吗啡以诱导在训练前吗啡影响下获得的记忆的状态依赖性恢复。在训练后5 min或测试前45 min给予L-NAME或L-精氨酸。结果：训练前吗啡诱导的记忆形成障碍是可逆的，而不是生理盐水的前测试吗啡。训练后给予L-精氨酸（200 mg/kg）和L-NAME（3、10和30 mg/kg）分别促进和损害记忆巩固，但测试前注射它们不影响记忆保持。然而，在训练后，L-精氨酸本身无效剂量20 mg/kg和60 mg/kg逆转吗啡诱导的记忆形成障碍。实验前给予L-NAME（3 mg/kg和10 mg/kg）可使吗啡所致的记忆障碍恢复，这种作用可被同时给予L-Arg（60 mg/kg）所阻断。试验前同时给予低剂量L-NAME（1 mg/kg）和吗啡（0.5 mg/kg）也显示了恢复吗啡记忆状态的累加效应。结论：这些结果提示，吗啡引起的记忆形成障碍和记忆再现易化与NO合成/释放减少有关，并可被NOS底物所抵消。
Rationale: Morphine and nitric oxide (NO) have important functional interactions in different neural processes, and both modulate learning and memory although their interaction in cognitive performance has not been elucidated. Objective: To examine the effect of the NO synthase (NOS) inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) and NOS substrate L-arginine on morphine-induced impairment of memory formation and the state-dependent retrieval of a passive avoidance task learned under morphine influence. Methods: All drugs were administered intraperitoneally, and a one-trial step-down paradigm was used for the assessment of memory in adult male NMRI mice. Morphine was administered 30 min before training to induce impairment of memory formation and 30 min before test to induce state-dependent retrieval of the memory acquired under pretraining morphine influence. L-NAME or L-arginine was administered either 5 min after training or 45 min before the test. Results: Pre-training morphine induced impairment of memory formation that was reversible by pre-test morphine but not saline. Post-training administration Of L-arginine (200 mg/kg) and L-NAME (3, 10 and 30 mg/kg), respectively, facilitated and impaired the memory consolidation, but their pre-test injections did not affect retention. However, post-training L-arginine at per se non-effective doses of 20 mg/kg and 60 mg/kg reversed the morphine-induced impairment of memory formation. Pretest administration Of L-NAME (3 mg/kg and 10 mg/kg) could restore the memory impairment induced by pretraining morphine, and this effect was blocked by concomitant pre-test L-arginine (60 mg/kg). Concomitant administration of low doses Of L-NAME (1 mg/kg) and morphine (0.5 mg/kg) pre-test also revealed an additive effect in restoring the morphine state of memory. Conclusion: These results suggest that the impairment of memory formation and the facilitation of retrieval induced by morphine involves decreased synthesis/release of NO and can be counteracted by NOS substrate.