The role of nitric oxide in dizocilpine-induced impairment of spontaneous alternation behavior in mice.
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.
Yamada
K
K
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Noda
Y
Y
Hasegawa
T
T
Komori
Y
Y
Nikai
T
T
Sugihara
H
H
Nabeshima
T
T
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006454:Hemoglobins / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D026423:S-Nitroso-N-Acetylpenicillamine; D013237:Stereoisomerism
D018691:Excitatory Amino Acid Antagonists; D006454:Hemoglobins; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D003995:Dibutyryl Cyclic GMP; D016291:Dizocilpine Maleate; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D010396:Penicillamine; D019331:NG-Nitroarginine Methyl Ester