Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of spontaneous alternation behavior in mice

K. Yamada, M. Hiramatsu, Y. Noda, T. Mamiya, M. Murai, T. Kameyama, Y. Komori, T. Nikai, H. Sugihara, Toshitaka Nabeshima

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

The activation of N-methyl-D-aspartate receptors induces the synthesis of nitric oxide, which activates soluble guanylate cyclase and leads to the formation of cyclic GMP in the brain. The inhibition of nitric oxide production, as well as the blockade of N-methyl-D-aspartate receptors, has been reported to prevent the induction of hippocampal long-term potentiation and learning and memory formation in vivo, although the effects of inhibitors of nitric oxide synthase are still controversial. We investigated the putative role of nitric oxide and cyclic GMP in dizocilpine-induced memory impairment in mice. The nitric oxide synthase inhibitors, N(G)- nitro-L-arginine methyl ester and 7-nitro indazole, as well as dizocilpine, a non competitive N-methyl-D-aspartate receptor antagonist, dose-dependently impaired spatial working memory in mice, assessed by their spontaneous alternation behavior in a Y-maze. The inhibitory effects of both N(G)- nitro-L-arginine methyl ester and dizocilpine on their behavior were completely reversed by 8-bromo-cyclic GMP. Cyclic GMP levels in the cerebellum were reduced by treatment with dizocilpine. N(G)-Nitro-L-arginine methyl ester and 7-nitro indazole reduced cyclic GMP levels in the cerebral cortex/hippocampus and cerebellum, and the suppressive effect of N(G)- nitro-L-arginine methyl ester on cyclic GMP levels in the cerebral cortex/hippocampus was reversed by co-treatment with L-arginine. Cyclic AMP levels in the brain were not affected by treatment with either dizocilpine, N(G)-nitro-L-arginine methyl ester, or 7-nitro indazole. Neither N(G)- nitro-L-arginine methyl ester nor L-arginine had any effect on monoamine and acetylcholine metabolism in the brain. These results suggest that the reduction in nitric oxide/cyclic GMP production in the brain may be responsible for dizocilpine-induced impairment of spontaneous alternation behavior in a Y-maze.

Original languageEnglish
Pages (from-to)365-374
Number of pages10
JournalNeuroscience
Volume74
Issue number2
DOIs
Publication statusPublished - 19-07-1996
Externally publishedYes

Fingerprint

Dizocilpine Maleate
NG-Nitroarginine Methyl Ester
Cyclic GMP
Nitric Oxide
N-Methyl-D-Aspartate Receptors
Brain
Nitric Oxide Synthase
Cerebral Cortex
Cerebellum
Hippocampus
Long-Term Memory
Long-Term Potentiation
Short-Term Memory
Cyclic AMP
Acetylcholine
Arginine
Learning
7-nitroindazole

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Yamada, K. ; Hiramatsu, M. ; Noda, Y. ; Mamiya, T. ; Murai, M. ; Kameyama, T. ; Komori, Y. ; Nikai, T. ; Sugihara, H. ; Nabeshima, Toshitaka. / Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of spontaneous alternation behavior in mice. In: Neuroscience. 1996 ; Vol. 74, No. 2. pp. 365-374.
@article{49b68ae9f9fb4b299f66d05a35c7b6a2,
title = "Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of spontaneous alternation behavior in mice",
abstract = "The activation of N-methyl-D-aspartate receptors induces the synthesis of nitric oxide, which activates soluble guanylate cyclase and leads to the formation of cyclic GMP in the brain. The inhibition of nitric oxide production, as well as the blockade of N-methyl-D-aspartate receptors, has been reported to prevent the induction of hippocampal long-term potentiation and learning and memory formation in vivo, although the effects of inhibitors of nitric oxide synthase are still controversial. We investigated the putative role of nitric oxide and cyclic GMP in dizocilpine-induced memory impairment in mice. The nitric oxide synthase inhibitors, N(G)- nitro-L-arginine methyl ester and 7-nitro indazole, as well as dizocilpine, a non competitive N-methyl-D-aspartate receptor antagonist, dose-dependently impaired spatial working memory in mice, assessed by their spontaneous alternation behavior in a Y-maze. The inhibitory effects of both N(G)- nitro-L-arginine methyl ester and dizocilpine on their behavior were completely reversed by 8-bromo-cyclic GMP. Cyclic GMP levels in the cerebellum were reduced by treatment with dizocilpine. N(G)-Nitro-L-arginine methyl ester and 7-nitro indazole reduced cyclic GMP levels in the cerebral cortex/hippocampus and cerebellum, and the suppressive effect of N(G)- nitro-L-arginine methyl ester on cyclic GMP levels in the cerebral cortex/hippocampus was reversed by co-treatment with L-arginine. Cyclic AMP levels in the brain were not affected by treatment with either dizocilpine, N(G)-nitro-L-arginine methyl ester, or 7-nitro indazole. Neither N(G)- nitro-L-arginine methyl ester nor L-arginine had any effect on monoamine and acetylcholine metabolism in the brain. These results suggest that the reduction in nitric oxide/cyclic GMP production in the brain may be responsible for dizocilpine-induced impairment of spontaneous alternation behavior in a Y-maze.",
author = "K. Yamada and M. Hiramatsu and Y. Noda and T. Mamiya and M. Murai and T. Kameyama and Y. Komori and T. Nikai and H. Sugihara and Toshitaka Nabeshima",
year = "1996",
month = "7",
day = "19",
doi = "10.1016/0306-4522(96)00161-3",
language = "English",
volume = "74",
pages = "365--374",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "2",

}

Yamada, K, Hiramatsu, M, Noda, Y, Mamiya, T, Murai, M, Kameyama, T, Komori, Y, Nikai, T, Sugihara, H & Nabeshima, T 1996, 'Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of spontaneous alternation behavior in mice', Neuroscience, vol. 74, no. 2, pp. 365-374. https://doi.org/10.1016/0306-4522(96)00161-3

Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of spontaneous alternation behavior in mice. / Yamada, K.; Hiramatsu, M.; Noda, Y.; Mamiya, T.; Murai, M.; Kameyama, T.; Komori, Y.; Nikai, T.; Sugihara, H.; Nabeshima, Toshitaka.

In: Neuroscience, Vol. 74, No. 2, 19.07.1996, p. 365-374.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of spontaneous alternation behavior in mice

AU - Yamada, K.

AU - Hiramatsu, M.

AU - Noda, Y.

AU - Mamiya, T.

AU - Murai, M.

AU - Kameyama, T.

AU - Komori, Y.

AU - Nikai, T.

AU - Sugihara, H.

AU - Nabeshima, Toshitaka

PY - 1996/7/19

Y1 - 1996/7/19

N2 - The activation of N-methyl-D-aspartate receptors induces the synthesis of nitric oxide, which activates soluble guanylate cyclase and leads to the formation of cyclic GMP in the brain. The inhibition of nitric oxide production, as well as the blockade of N-methyl-D-aspartate receptors, has been reported to prevent the induction of hippocampal long-term potentiation and learning and memory formation in vivo, although the effects of inhibitors of nitric oxide synthase are still controversial. We investigated the putative role of nitric oxide and cyclic GMP in dizocilpine-induced memory impairment in mice. The nitric oxide synthase inhibitors, N(G)- nitro-L-arginine methyl ester and 7-nitro indazole, as well as dizocilpine, a non competitive N-methyl-D-aspartate receptor antagonist, dose-dependently impaired spatial working memory in mice, assessed by their spontaneous alternation behavior in a Y-maze. The inhibitory effects of both N(G)- nitro-L-arginine methyl ester and dizocilpine on their behavior were completely reversed by 8-bromo-cyclic GMP. Cyclic GMP levels in the cerebellum were reduced by treatment with dizocilpine. N(G)-Nitro-L-arginine methyl ester and 7-nitro indazole reduced cyclic GMP levels in the cerebral cortex/hippocampus and cerebellum, and the suppressive effect of N(G)- nitro-L-arginine methyl ester on cyclic GMP levels in the cerebral cortex/hippocampus was reversed by co-treatment with L-arginine. Cyclic AMP levels in the brain were not affected by treatment with either dizocilpine, N(G)-nitro-L-arginine methyl ester, or 7-nitro indazole. Neither N(G)- nitro-L-arginine methyl ester nor L-arginine had any effect on monoamine and acetylcholine metabolism in the brain. These results suggest that the reduction in nitric oxide/cyclic GMP production in the brain may be responsible for dizocilpine-induced impairment of spontaneous alternation behavior in a Y-maze.

AB - The activation of N-methyl-D-aspartate receptors induces the synthesis of nitric oxide, which activates soluble guanylate cyclase and leads to the formation of cyclic GMP in the brain. The inhibition of nitric oxide production, as well as the blockade of N-methyl-D-aspartate receptors, has been reported to prevent the induction of hippocampal long-term potentiation and learning and memory formation in vivo, although the effects of inhibitors of nitric oxide synthase are still controversial. We investigated the putative role of nitric oxide and cyclic GMP in dizocilpine-induced memory impairment in mice. The nitric oxide synthase inhibitors, N(G)- nitro-L-arginine methyl ester and 7-nitro indazole, as well as dizocilpine, a non competitive N-methyl-D-aspartate receptor antagonist, dose-dependently impaired spatial working memory in mice, assessed by their spontaneous alternation behavior in a Y-maze. The inhibitory effects of both N(G)- nitro-L-arginine methyl ester and dizocilpine on their behavior were completely reversed by 8-bromo-cyclic GMP. Cyclic GMP levels in the cerebellum were reduced by treatment with dizocilpine. N(G)-Nitro-L-arginine methyl ester and 7-nitro indazole reduced cyclic GMP levels in the cerebral cortex/hippocampus and cerebellum, and the suppressive effect of N(G)- nitro-L-arginine methyl ester on cyclic GMP levels in the cerebral cortex/hippocampus was reversed by co-treatment with L-arginine. Cyclic AMP levels in the brain were not affected by treatment with either dizocilpine, N(G)-nitro-L-arginine methyl ester, or 7-nitro indazole. Neither N(G)- nitro-L-arginine methyl ester nor L-arginine had any effect on monoamine and acetylcholine metabolism in the brain. These results suggest that the reduction in nitric oxide/cyclic GMP production in the brain may be responsible for dizocilpine-induced impairment of spontaneous alternation behavior in a Y-maze.

UR - http://www.scopus.com/inward/record.url?scp=0030593430&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030593430&partnerID=8YFLogxK

U2 - 10.1016/0306-4522(96)00161-3

DO - 10.1016/0306-4522(96)00161-3

M3 - Article

C2 - 8865189

AN - SCOPUS:0030593430

VL - 74

SP - 365

EP - 374

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 2

ER -