Yamada K, Noda Y, Hasegawa T, Komori Y, Nikai T, Sugihara H, Nabeshima T
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
J Pharmacol Exp Ther. 1996 Feb;276(2):460-6.
We investigated the role played by nitric oxide in the dizocilpine-induced impairment of both spontaneous alternation behavior in a Y-maze and of performance in a multiple-trial passive avoidance task in mice. Dizocilpine (0.1 mg/kg) impaired the spontaneous alternation behavior and the retention of passive avoidance without affecting acquisition in the multiple-trial passive avoidance task. NG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide (NO) synthase, dose-dependently impaired the spontaneous alternation behavior, but had no effect on either the acquisition or retention of passive avoidance. NG-nitro-D-arginine methylester had no effect on either task. The inhibitory effect of L-NAME on the spontaneous alternation behavior was completely reversed by the coadministration of L-arginine. Pretreatment with L-arginine ameliorated the dizocilpine-induced impairment of spontaneous alternation behavior, but not the impairment of the retention of passive avoidance. S-Nitroso-N-acetylpenicillamine, a generator of NO, completely inhibited the dizocilpine-induced impairment of spontaneous alternation behavior. Finally, the impairment of spontaneous alternation behavior caused by dizocilpine was significantly diminished by pretreatment with dibutyryl cyclic GMP. These results suggest that, although N-methyl-D-aspartate receptors play a critical role in both spatial working memory and long-term memory processes assessed by spontaneous alternation behavior and the passive avoidance, respectively, different neuronal mechanisms may be involved in these two processes. Further, it is suggested that the NO/cyclic GMP system may play a role in spatial working memory.
我们研究了一氧化氮在二氮嗪诱导的小鼠Y迷宫自发交替行为及多次试验被动回避任务表现受损中所起的作用。二氮嗪（0.1毫克/千克）损害了自发交替行为和被动回避的记忆保持，而不影响多次试验被动回避任务中的习得。一氧化氮（NO）合酶抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）剂量依赖性地损害自发交替行为，但对被动回避的习得或记忆保持均无影响。NG-硝基-D-精氨酸甲酯对这两项任务均无影响。L-精氨酸的共同给药完全逆转了L-NAME对自发交替行为的抑制作用。L-精氨酸预处理改善了二氮嗪诱导的自发交替行为损害，但未改善被动回避记忆保持的损害。NO生成剂S-亚硝基-N-乙酰青霉胺完全抑制了二氮嗪诱导的自发交替行为损害。最后，用二丁酰环磷鸟苷预处理可显著减轻二氮嗪引起的自发交替行为损害。这些结果表明，虽然N-甲基-D-天冬氨酸受体分别在通过自发交替行为和被动回避评估的空间工作记忆和长期记忆过程中起关键作用，但这两个过程可能涉及不同的神经元机制。此外，提示NO/环磷鸟苷系统可能在空间工作记忆中起作用。
