Harooni Hooman Eshagh, Naghdi Nasser, Sepehri Hoori, Rohani Ali Haeri
Department of Physiology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
Behav Brain Res. 2009 Jul 19;201(1):166-72. doi: 10.1016/j.bbr.2009.02.011. Epub 2009 Feb 21.
There is impressive amount of evidence suggesting the involvement of nitric oxide (NO) in hippocampal synaptic plasticity and consequently learning and memory. Hippocampus is a brain region which is widely implicated in several types of learning and memory formation, including inhibitory avoidance learning. Since the CA1 region of hippocampus has shown nitric oxide synthase (NOS) activity, inhibition of the NOS enzymes can modulate hippocampal function, hence affecting memory processes. Therefore, we conducted series of experiments to further investigate the role of NO on inhibitory avoidance short- and long-term memory in rats. For this purpose, male Wistar rats were divided into 15 groups (n=10), and bilaterally implanted with guide cannulae aimed at the CA1 region of hippocampus. Animals received pre-training, post-training and pre-retrieval injections of vehicle (saline) or different doses of L-NAME (5, 10 and 15 microg/0.5 microl/side) or l-arginine (alone or in combination with L-NAME), tested for immediate, short- and long-term memory retention in an inhibitory avoidance task. Our results indicated that step-through latency (STL) of short- and long-term memory retention test was significantly reduced in L-NAME treated rats (15 microg/0.5 microl for immediate and short-term memory; 10 microg/0.5 microl for long-term memory), as compared to that of control group. Results also revealed that, L-arginine produced no any significant effect on STL, however could reverse the effect of L-NAME on memory. Our results also showed that, blocking of NO signaling immediately after training had no effect on either short- or long-term memory, indicating that NO release only during training, and not during consolidation, plays a role in memory formation. Together, our findings suggest that NO synthase inhibition by L-NAME can induce impairments in immediate, short- and long-term memories of inhibitory avoidance task, and these impairments are dependent on the learning and memory processes at which NOS inhibited.
有大量令人印象深刻的证据表明一氧化氮（NO）参与海马体突触可塑性，进而影响学习和记忆。海马体是一个广泛参与多种类型学习和记忆形成的脑区，包括抑制性回避学习。由于海马体的CA1区已显示出一氧化氮合酶（NOS）活性，抑制NOS酶可调节海马体功能，从而影响记忆过程。因此，我们进行了一系列实验，以进一步研究NO对大鼠抑制性回避短期和长期记忆的作用。为此，将雄性Wistar大鼠分为15组（每组n = 10），并双侧植入针对海马体CA1区的引导套管。动物接受训练前、训练后和检索前注射载体（生理盐水）或不同剂量的L - NAME（5、10和15微克/0.5微升/侧）或L - 精氨酸（单独或与L - NAME联合使用），并在抑制性回避任务中测试即时、短期和长期记忆保持情况。我们的结果表明，与对照组相比，L - NAME处理的大鼠（即时和短期记忆为15微克/0.5微升；长期记忆为10微克/0.5微升）在短期和长期记忆保持测试中的穿通潜伏期（STL）显著缩短。结果还显示，L - 精氨酸对STL没有任何显著影响，但可以逆转L - NAME对记忆的影响。我们的结果还表明，训练后立即阻断NO信号对短期或长期记忆均无影响，这表明NO仅在训练期间释放，而在巩固期间不释放，在记忆形成中起作用。总之，我们的研究结果表明，L - NAME抑制NO合酶可导致抑制性回避任务的即时、短期和长期记忆受损，并且这些损伤取决于NOS被抑制时的学习和记忆过程。
