Effects of olanzapine, sertindole and clozapine on learning and memory in the Morris water maze test in naive and MK-801-treated mice

• Published in: Pharmacology, biochemistry and behavior Vol. 98; no. 3; pp. 398 - 404
• Main Authors: Mutlu, Oguz, Ulak, Güner, Celikyurt, Ipek Komsuoglu, Akar, Füruzan Yıldız, Erden, Faruk
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Inc 01-05-2011; Elsevier
• Subjects: Animals; Antipsychotic Agents - pharmacology; Antipsychotics; Benzodiazepines - pharmacology; Biological and medical sciences; Clozapine - pharmacology; Cognition; Dizocilpine Maleate - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Imidazoles - pharmacology; Indoles - pharmacology; Learning - drug effects; Male; Maze Learning; Medical sciences; Memory - drug effects; Mice; Mice, Inbred BALB C; MK-801; Morris water maze; Neuropharmacology; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Antipsychotics; MK-801; Cognition; Mice; Morris water maze; Dibenzodiazepine derivatives; Atypical antipsychotic; Olanzapine; Neuroleptic; Psychotropic; Memory; Pharmacotherapy; Glutamate receptor; Space perception; Serotonine receptor; Sertindole; Dopamine antagonist; Serotonin antagonist; Dizocilpine; Rodentia; Neuroprotective agent; Clozapine; Thienobenzodiazepine derivatives; Vertebrata; Mammalia; D2 Dopamine receptor; Treatment; Mouse; Animal; Perceptive learning; NMDA receptor
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2011.02.009

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.
► MK-801 induced marked cognitive deficits in mice. ► Olanzapine had some disturbing effects on cognition in naive animals. ► Olanzapine, sertindole and clozapine had beneficial effects in MK-801-treated mice.