title: Effects of olanzapine, sertindole and clozapine on learning and memory in the Morris water maze test in naive and MK-801-treated mice.
abstract: Cognitive dysfunction in schizophrenia is associated with functional disease symptoms. The beneficial effects of second generation antipsychotic drugs on cognitive function in schizophrenic patients are controversial. In this study, we investigated the effects of the second generation antipsychotics olanzapine, sertindole and clozapine on cognitive function in the Morris water maze task in naive or MK-801-treated animals. Male balb-c mice were treated subchronically with olanzapine (1.25, 2.5 and 5mg/kg, i.p.), sertindole (0.63, 1.3, 2.5mg/kg, s.c.) or clozapine (0.5 and 1mg/kg, i.p.), and cognitive deficits were induced by MK-801 (0.2mg/kg, i.p.) administration. Water maze performance was expressed as escape latency to find the hidden platform, the time spent in target quadrant, the mean distance to platform and the swim speed. In naive mice olanzapine impaired water maze performance, whereas sertindole and clozapine had no effect while the MK-801-induced cognitive impairment was reversed by the second generation antipsychotics - olanzapine, sertindole and clozapine at the doses used. These results revealed that while olanzapine had some disturbing effects on cognitive functions in naive animals; olanzapine, sertindole and clozapine might improve cognitive deficits in schizophrenic patients.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kocaeli University, 41380 Kocaeli, Turkey. oguzmutlu80@hotmail.com
authors.forename: Oguz
authors.initials: O
authors.lastname: Mutlu
authors.forename: Güner
authors.initials: G
authors.lastname: Ulak
authors.forename: Ipek Komsuoglu
authors.initials: IK
authors.lastname: Celikyurt
authors.forename: Füruzan Yildiz
authors.initials: FY
authors.lastname: Akar
authors.forename: Faruk
authors.initials: F
authors.lastname: Erden
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D000077152:Olanzapine
chemical_list: D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; D007211:Indoles; D001569:Benzodiazepines; D016291:Dizocilpine Maleate; C066304:sertindole; D003024:Clozapine; D000077152:Olanzapine