PT - JOURNAL ARTICLE AU - K Yamada AU - Y Noda AU - T Hasegawa AU - Y Komori AU - T Nikai AU - H Sugihara AU - T Nabeshima TI - The role of nitric oxide in dizocilpine-induced impairment of spontaneous alternation behavior in mice. DP - 1996 Feb 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 460--466 VI - 276 IP - 2 4099 - http://jpet.aspetjournals.org/content/276/2/460.short 4100 - http://jpet.aspetjournals.org/content/276/2/460.full SO - J Pharmacol Exp Ther1996 Feb 01; 276 AB - 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.