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

K Yamada, Y Noda, T Hasegawa, Y Komori, T Nikai, H Sugihara and T Nabeshima

Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.

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.

Volume 276, Issue 2, pp. 460-466, 02/01/1996
Copyright © 1996 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1996 by the American Society for Pharmacology and Experimental Therapeutics.