Effects of olanzapine, sertindole and clozapine on MK-801 induced visual memory deficits in mice

• Published in: Pharmacology, biochemistry and behavior Vol. 99; no. 4; pp. 557 - 565
• Main Authors: Mutlu, Oguz, Ulak, Güner, Celikyurt, Ipek Komsuoglu, Akar, Füruzan Yıldız, Erden, Faruk, Tanyeri, Pelin
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Inc 01-10-2011; Elsevier
• Subjects: Animals; Antipsychotic Agents - pharmacology; Atypical antipsychotics; Benzodiazepines - pharmacology; Biological and medical sciences; Clozapine - pharmacology; Cognition; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Imidazoles - pharmacology; Indoles - pharmacology; Learning - drug effects; Male; Medical sciences; Memory Disorders - chemically induced; Memory Disorders - drug therapy; Memory Disorders - psychology; Mice; Mice, Inbred BALB C; MK-801; Motor Activity - drug effects; Neuropharmacology; Novel object recognition test; Open field test; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Recognition (Psychology) - drug effects; Visual Perception - drug effects; MK-801; Atypical antipsychotics; Cognition; Mice; Novel object recognition test; Open field test; Memory disorder; Dibenzodiazepine derivatives; Cognitive disorder; Atypical antipsychotic; Olanzapine; Neuroleptic; Psychotropic; Vision disorder; Glutamate receptor; Serotonine receptor; Sertindole; Visual memory; Dopamine antagonist; Serotonin antagonist; Dizocilpine; Rodentia; Neuroprotective agent; Clozapine; Novelty stimulus; Thienobenzodiazepine derivatives; Open field behavior; Eye disease; Vertebrata; Mammalia; D2 Dopamine receptor; Mouse; Animal; NMDA receptor; Recognition
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2011.06.011

We investigated the effects of the second generation antipsychotics olanzapine, sertindole and clozapine on visual recognition memory using the novel object recognition (NOR) test in naive and MK-801-treated animals. The effects of drug treatment on locomotion and anxiety were also determined using the open field test.
Male Balb-c mice were treated with olanzapine (0.2, 0.4 and 0.6mg/kg; i.p.), sertindole (0.63, 1.3 and 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. Olanzapine treatment decreased the ratio index in the NOR test, whereas sertindole and clozapine had no effect in naive mice. MK-801-induced cognitive impairment was reversed by treatment with olanzapine, sertindole or clozapine. While olanzapine, sertindole and clozapine had no effect on the anxiety of naive mice as determined by the open field test, MK-801 significantly increased the total distance traveled, time spent in the center zone and the velocity of the animals. MK-801-induced effects on locomotion and anxiety in the open field test were reversed by olanzapine, sertindole or clozapine treatment. The results of the present study demonstrated that olanzapine, sertindole and clozapine improved cognition in MK-801 treated mice, and indicate that these drugs have a potential to improve cognition in schizophrenia.
► 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.