title: Effects of the inducible nitric oxide synthase inhibitor aminoguanidine in two different rat models of schizophrenia.
abstract: Several lines evidence indicate that the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist ketamine and the mixed dopamine (DA) D1/D2 receptor agonist apomorphine induce schizophrenia-like symptoms in rodents, including memory impairments and social withdrawal. Nitric oxide (NO) has been proposed to act as an intracellular messenger in the brain and its overproduction is associated with schizophrenia. The current study was designed to investigate the ability of the inducible NO synthase (iNOS) inhibitor aminoguanidine (AG) to counteract schizophrenia-like behavioural deficits produced by ketamine and apomorphine in rats. The efficacy of AG to antagonize extinction of recognition memory, ketamine and apomorphine-induced recognition memory impairments was tested utilizing the novel object recognition task (NORT). Further, the efficacy of AG to attenuate ketamine-induced social withdrawal was examined in the social interaction test. AG (25 and 50mg/kg) antagonized extinction of recognition memory and reversed ketamine (3mg/kg) and apomorphine (1mg/kg)-induced recognition memory deficits. In contrast, AG (50 and 100mg/kg) did not counteract the ketamine (8mg/kg)-induced social isolation. The present data show that the iNOS inhibitor AG counteracted extinction of recognition memory and reversed recognition memory deficits produced by dysfunction of the glutamatergic and the dopaminergic (DAergic) system in rats. Therefore, AG may be efficacious in attenuating memory impairments often observed in schizophrenia patients.
authors.affiliation: Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Thessaly, Larissa, Greece.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Lafioniatis
authors.affiliation: Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Thessaly, Larissa, Greece.
authors.forename: Martha A
authors.initials: MA
authors.lastname: Orfanidou
authors.affiliation: Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Thessaly, Larissa, Greece.
authors.forename: Evangelia S
authors.initials: ES
authors.lastname: Papadopoulou
authors.affiliation: Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Thessaly, Larissa, Greece. Electronic address: npitsikas@med.uth.gr.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Pitsikas
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D007649:Ketamine; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy* / Q000201:enzymology; D012565:Schizophrenic Psychology; D012919:Social Behavior
chemical_list: D014150:Antipsychotic Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D007649:Ketamine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001058:Apomorphine; C004479:pimagedine
keywords: Aminoguanidine; Apomorphine; Ketamine; Nitric oxide; Schizophrenia