Inhibition of nitric oxide synthase does not impair spatial learning
Inhibition of nitric oxide synthase does not impair spatial learning
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抑制一氧化氮合酶不会损害空间学习
DOI：
10.1523/jneurosci.14-12-07404.1994
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发表时间：
1994
期刊：
影响因子：
6.2
通讯作者：
R. Morris
中科院分区：
文献类型：
--
作者：
D. Bannerman;PF Chapman;P. Kelly;S. Butcher;R. Morris
一氧化氮(NO)是中枢神经系统中的一种细胞间信使，可能参与某些形式的突触可塑性和学习。本文报道了N-奥米伽-硝基-L-精氨酸甲酯(L-NAME)对水迷宫各种形式学习记忆的影响。L-NAME(75 mg/kg，ip，足以使脑内NO合成抑制90%)在习得期间(3d，每天6次训练)给幼鼠造成明显的空间学习障碍。这种损害是剂量相关的、立体选择性的，并通过联合应用L-精氨酸来减轻。第二项研究表明，L的名字并不影响对先前学习的空间任务的保持。此外，在视觉辨别任务中，达到标准水平的速度不受L名字的影响。因此，抑制一氧化氮合酶可能导致空间学习的选择性损害，而不影响保持能力。然而，对视觉辨别任务的早期训练试验的分析显示，L处理的大鼠的逃避潜伏期显著延长，这表明抑制一氧化氮合酶可能具有更普遍的影响。由于正常大鼠学习空间任务的速度非常快，有可能学习的明显缺陷是由于学习本身以外的某些过程的中断造成的。进一步的一系列实验研究了这种可能性。研究发现，L的名字不会影响在相同空间环境中学习新的平台位置。令人惊讶的是，L在第二个水迷宫中也没有影响到大鼠在一个新的空间环境中的空间学习，这些大鼠接受了所有方面的水迷宫训练。最后，L的名字对每天只训练一次的幼稚大鼠的空间学习没有影响。因此，系统注射一氧化氮合酶抑制剂会在两个任务的初始习得过程中损害其行为表现，但这种功能障碍的基础不太可能是由于对空间学习机制的任何直接影响。
Nitric oxide (NO), a putative intercellular messenger in the CNS, may be involved in certain forms of synaptic plasticity and learning. This article reports a series of experiments investigating the effects of N omega-nitro-L-arginine methyl ester (L-NAME) upon various forms of learning and memory in the watermaze. L-NAME (75 mg/kg, i.p., sufficient to bring about > 90% inhibition of NO synthesis in brain) produced an apparent impairment in spatial learning when given to naive rats during acquisition (3 d, six training trials per day). This impairment was dose related, stereoselective, and attenuated by coadministration of L-arginine. A second study showed that L-NAME did not affect the retention of a previously learned spatial task. In addition, in a visual discrimination task, the rate at which criterion levels of performance were reached was unaffected by L-NAME. Thus, inhibition of NO synthase may cause a selective impairment of spatial learning without effect upon retention. However, analysis of the early training trials of the visual discrimination task revealed significantly elevated escape latencies in the L-NAME-treated rats, suggesting that inhibition of NO synthase may have more general effects. As normal rats learn the spatial task very rapidly, the possibility arises that the apparent deficit in learning is due to a disruption of some process other than learning per se. A further series of experiments investigated this possibility. L-NAME was found not to impair the learning of a new platform position in the same spatial environment. Surprisingly, L-NAME also had no effect on spatial learning in a second watermaze located in a novel spatial environment by rats well practiced with all aspects of watermaze training. Finally, L-NAME had no effect on spatial learning in naive rats trained with just one trial per day. Thus, systemic injection of an NO synthase inhibitor impairs behavioral performance in two tasks during their initial acquisition, but the basis of this functional disruption is unlikely to be due to any direct effect upon the mechanisms of spatial learning.
DOI：
10.1073/pnas.88.24.11285
发表时间：
1991-12-01
影响因子：
11.1
作者：
ODELL, TJ;HAWKINS, RD;ARANCIO, O
通讯作者：
ARANCIO, O