title: 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.
abstract: 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.
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, 466-8560, Nagoya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mamiya
authors.forename: Y
authors.initials: Y
authors.lastname: Noda
authors.forename: A
authors.initials: A
authors.lastname: Noda
authors.forename: M
authors.initials: M
authors.lastname: Hiramatsu
authors.forename: K
authors.initials: K
authors.lastname: Karasawa
authors.forename: T
authors.initials: T
authors.lastname: Kameyama
authors.forename: S
authors.initials: S
authors.lastname: Furukawa
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Nabeshima
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010423:Pentazocine / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D017480:Receptors, sigma / Q000819:agonists*
chemical_list: D000701:Analgesics, Opioid; D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D007191:Indazoles; D011743:Pyrimidines; D017480:Receptors, sigma; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; C012134:SK&F 10047; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D006152:Cyclic GMP; D010620:Phenazocine; C050232:1,3-ditolylguanidine; D010423:Pentazocine; D008751:Methylene Blue; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester