The role of nitric oxide in dizocilpine-induced impairment of spontaneous alternation behavior in mice

Kiyofumi Yamada, Yukihiro Noda, Takaaki Hasegawa, Yumiko Komori, Toshiaki Nikai, Hisayoshi Sugihara, Toshitaka Nabeshima

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Abstract

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-o-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.

Original languageEnglish
Pages (from-to)460-466
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume276
Issue number2
Publication statusPublished - 01-02-1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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    Yamada, K., Noda, Y., Hasegawa, T., Komori, Y., Nikai, T., Sugihara, H., & Nabeshima, T. (1996). The role of nitric oxide in dizocilpine-induced impairment of spontaneous alternation behavior in mice. Journal of Pharmacology and Experimental Therapeutics, 276(2), 460-466.