Effects of sigma receptor agonists on the impairment of spontaneous alternation behavior and decrease of cyclic GMP level induced by nitric oxide synthase inhibitors in mice

• Published in: Neuropharmacology 2000-11, Vol.39 (12), p.2391-2398
• Main Authors: Mamiya, Takayoshi, Noda, Yukihiro, Noda, Akihiro, Hiramatsu, Masayuki, Karasawa, Katsuhiro, Kameyama, Tsutomu, Furukawa, Shoei, Yamada, Kiyofumi, Nabeshima, Toshitaka
• Format: Article
• Language: English
• Subjects: Analgesics, Opioid - pharmacology; Animal; Animals; Anti-Anxiety Agents - pharmacology; Antipsychotic Agents - pharmacology; Behavior, Animal - drug effects; Biological and medical sciences; Brain Chemistry - drug effects; Cell receptors; Cell structures and functions; Cyclic GMP; Cyclic GMP - metabolism; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Guanidines - pharmacology; Indazoles - pharmacology; Learning. Memory; Male; Medical sciences; Memory; Methylene Blue - pharmacology; Mice; Miscellaneous; Molecular and cellular biology; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric oxide synthase inhibitor; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Nitric oxide/cyclic GMP pathway; Pentazocine - pharmacology; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Phenazocine - analogs & derivatives; Phenazocine - pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Pyrimidines - pharmacology; Receptors, sigma - agonists; Sigma receptor agonists; Spontaneous alternation behavior
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(00)00078-2

In this study, we investigated the involvement of the interaction between sigma receptors and the nitric oxide/cyclic GMP pathway in short term memory in mice, assessed through spontaneous alternation behavior in a Y-maze. N G-Nitro-L-arginine methyl ester and 7-nitro indazole, both nitric oxide synthase inhibitors, impaired the spontaneous alternation behavior. These impairments were attenuated by (+) SKF 10,047 and (+) pentazocine, sigma 1 receptor agonists. Further, the sigma 1 receptor antagonist, NE-100, reversed the improvements made by sigma receptor agonists. Cyclic GMP levels and nitric oxide synthase activity in the hippocampus were reduced by treatment with N G-nitro-L-arginine methyl ester. The suppressive effects of N G-nitro-L-arginine methyl ester on the cyclic GMP levels were reversed by co-treatment with (+) SKF 10,047, but the decline in nitric oxide synthase activity was not. These results suggest that the nitric oxide/cyclic GMP pathway in the hippocampus is responsible for spontaneous alternation behavior in a Y-maze. Further, the ameliorating effects of (+) SKF 10,047 on the impairment of spontaneous alternation behavior may be mediated through activation of guanylate cyclase, but not nitric oxide synthase in the hippocampus of mice.