Effects of Olanzapine and Clozapine on Radial Maze Performance in Naive and MK-801-Treated Mice

Abstract

Attention, working memory and long-term memory dysfunctions are the most commonly seen cognitive impairments in schizophrenic patients. Conflicting results exist regarding the effects of antipsychotics on cognitive abnormalities. The aim of this study was to investigate the effects of atypical antipsychotic drugs olanzapine (0.4, 0.8 and 1.25 mg/kg, i.p.) and clozapine (0.5 and 1 mg/kg, i.p.) on spatial working memory in naive and MK-801 (0.2 mg/kg, i.p.) treated BALB-c mice in an 8-arm radial arm maze (RAM) task. None of the antipsychotic drugs studied altered number of errors in naive mice, whereas MK-801 significantly increased working memory errors in RAM test. Olanzapine and clozapine potently reversed MK-801 induced increasement of working memory errors. Olanzapine and clozapine prolonged latency of the animals in naive mice. The MK-801-induced enhancement in the speed of mice in performing the RAM task was blocked by olanzapine but not clozapine. Our study shows that atypical antipsychotics olanzapine and clozapine might improve cognitive deficits in schizophrenic patients.

Key words

atypical antipsychotics - MK-801 - mice - radial arm maze task - spatial memory

• References

• 1 Green MF, Kern RS, Braff DL et al. Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the “right stuff”?. Schizophr Bull 2000; 26: 119-136
• 2 Green MF, Nuechterlein KH, Gold JM et al. Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria. Biol Psychiatry 2004; 56: 301-307
• 3 Harvey PD, Green MF, Keefe RS et al. Cognitive functioning in schizophrenia: a consensus statement on its role in the definition and evaluation of effective treatments for the illness. J Clin Psychiatry 2004; 65: 361-372
• 4 Didriksen M, Skarsfeldt T, Arnt J. Reversal of PCP-induced learning and memory deficits in the Morris’ water maze by sertindole and other antipsychotics. Psychopharmacology 2007; 193: 225-233
• 5 Mortimer AM. Cognitive function in schizophrenia – do neuroleptics make a difference?. Pharmacol Biochem Behav 1997; 56: 789-795
• 6 Cleghorn JM, Kaplan RD, Szechtman B et al. Neuroleptic drug effects on cognitive function in schizophrenia. Schizophr Res 1990; 3: 211-219
• 7 Fulton B, Goa KL. Olanzapine, a review of its pharmacological properties and therapeutic efficacy in the management of schizophrenia and related psychoses. Drugs 1997; 53: 281-298
• 8 Kane JM, Tamminga CA. Sertindole (serdolect): preclinical and clinical findings of a new atypical antipsychotic. Exp Opin Invest Drugs 1997; 6: 1729-1741
• 9 Krystal JH, Karper LP, Seibyl JP et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 1994; 51: 199-214
• 10 Jafari-Sabet M. NMDA receptor antagonists antagonize the facilitatory effects of post-training intra-basolateral amygdala NMDA and physostigmine on passive avoidance learning. Eur J Pharmacol 2006; 529: 122-128
• 11 Harvey PD, Kefe RS. Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry 2001; 158: 176-184
• 12 Goldberg TE, Greenberg RD, Griffin SJ et al. The effect of clozapine on cognition and psychiatric symptoms in patients with schizophrenia. Br J Psychiatry 1993; 162: 43-48
• 13 Meltzer HY, McGurk SR. The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull 1999; 25: 233-255
• 14 Hoff AL, Faustman WO, Wieneke M et al. The effect of clozapine on symptom reduction, neurocognitive function, and clinical management in treatment-refractory state hospital schizophrenic inpatients. Neuropsychopharmacology 1996; 15: 361-369
• 15 Beuzen A, Belzung C, Roullet P. Drug effects in a radial maze designed for dissociation of cues used by mice. Pharmacol Biochem Behav 1994; 48: 23-29
• 16 Belzung C, Le Guisquet AM, Griebel G. b-CCT, a selective BZ-v receptor antagonist, blocks the anti-anxiety but not the amnesic action of chlordiazepoxide in mice. Behav Pharmacol 2000; 11: 125-131
• 17 Didriksen M, Kreilgaard M, Arnt J. Sertindole, in contrast to clozapine and olanzapine, does not disrupt water maze performance after acute or chronic treatment. Eur J Pharmacol 2006; 542: 108-115
• 18 Skarsfeldt T. Differential effect of antipsychotics on place navigation of rats in the Morris water maze. Psychopharmacology 1996; 124: 126-133
• 19 Nagai T, Kamei H, Dohniwa M et al. Involvement of hippocampal extracellular signal-regulated kinase 1/2 in spatial working memory in rats. Neuroreport 2006; 17: 1453-1457
• 20 Suzuki S, Augerinos G, Black AH. Stimulus control of spatial behavior on the eight-arm maze in rats. Learn Motiv 1980; 11: 1-18
• 21 Zou LB, Yamada K, Nabeshima T. Sigma receptor ligands (+)- SKF10,047 and SA4503 improve dizocilpine-induced spatial memory deficits in rats. Eur J Pharmacol 1998; 355: 1-10
• 22 Lee MA, Jayathilake K, Meltzer HY. A comparison of effect of clozapine with typical neuroleptics on cognitive function in neuroleptic-responsive schizophrenia. Schizoph Res 1999; 37: 1-12
• 23 Jentsch JD, Tran A, Le D et al. Sub-chronic phencyclidine administration reduces mesoprefrontal dopamine utilization and impairs prefrontal cortical-dependent cognition in the rat. Neuropsychopharmacology 1997; 17: 92-99
• 24 Didriksen M. Effects of antipsychotics on cognitive behaviour in rats using the delayed non-match to position paradigm. Eur J Pharmacol 1995; 281: 241-250
• 25 Enomoto T, Ishibashi T, Tokuda K et al. Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats. Behav Brain Res 2008; 186: 197-207
• 26 Bymaster F, Perry KW, Nelson DL et al. Olanzapine: a basic science update. Br J Psychiatry Suppl 1999; 37: 36-40
• 27 He H, Richardson JS. A pharmacological, pharmacokinetic and clinical overview of risperidone, a new antipsychotic that blocks serotonin 5-HT2 and dopamine D2 receptors. Int Clin Psychopharmacol 1995; 10: 19-30
• 28 Stephenson CM, Pilowsky LS. Psychological of olanzapine. A review. Br J Psychiatry 1999; 38: 52-58
• 29 Schotte A, Janssen PF, Gommeren W et al. Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology 1996; 124: 57-73
• 30 Terry Jr AV, Buccafusco JJ, Bartoszyk GD. Selective serotonin 5-HT2A receptor antagonist EMD 281014 improves delayed matching performance in young and aged rhesus monkeys. Psychopharmacology (Berl) 2005; 179: 725-732
• 31 Winstanley CA, Chudasama Y, Dalley JW et al. Intra-prefrontal 8-OH-DPAT and M100907 improve visuospatial attention and decrease impulsivity on the five-choice serial reaction time task in rats. Psychopharmacology (Berl) 2003; 167: 304-314
• 32 Li XM, Perry KW, Wong DT et al. Olanzapine increases in vivo dopamine and norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum. Psychopharmacology 1998; 136: 153-161
• 33 Bymaster FP, Falcone JF, Bauzon D et al. Potent antagonism of 5-HT(3) and 5-HT(6) receptors by olanzapine. Eur J Pharmacol 2001; 430: 341-349
• 34 Rogers DC, Robinson TL, Quilter CA et al. Cognitive enhancement effects of the selective 5-HT6 antagonist SB-271046. Br J Pharmacol 1999; 127: 22
• 35 Dawson LA, Huy O, Nguyen BS et al. The 5-HT6 receptor antagonist SB- 271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus. Neuropsychopharmacology 2001; 25: 662-668
• 36 Okamura N, Yanai K, Higuchi M et al. Functional neuroimaging of cognition impaired by a classical antihistamine, D-chlorpheniramine. Br J Pharmacol 2000; 129: 115-123
• 37 Tashiro M, Mochizuki H, Iwabuchi K et al. Roles of histamine in regulation of arousal and cognition: functional neuroimaging of histamine H1 receptors in human brain. Life Sci 2002; 72: 409-414
• 38 Altar CA, Wasley AM, Neale RF et al. Typical and atypical antipsychotic occupancy of D2 and S2 receptors: an autoradiographic analysis in rat brain. Brain Res Bull 1986; 16: 517-525
• 39 Lipska BK, Weinberger DR. To model a psychiatric disorder in animals: schizophrenia as a reality test. Neuropsychopharmacology 2000; 23: 223-239
• 40 Abdul-Monim Z, Reynolds GP, Neill JC. The atypical antipsychotic ziprasidone, but not haloperidol, improves phencyclidine-induced cognitive deficits in a reversal learning task in the rat. J Psychopharmacol 2003; 17: 57-65
• 41 Cartmell J, Monn JA, Schoepp DD. Attenuation of specific PCP-evoked behaviors by the potent mGlu2/3 receptor agonist, LY379268 and comparison with the atypical antipsychotic, clozapine. Psychopharmacology (Berl) 2000; 148: 423-429
• 42 Gleason SD, Shannon HE. Blockade of phencyclidine-induced hyperlocomotion by olanzapine, clozapine and serotonin receptor subtype selective antagonists in mice. Psychopharmacology 1997; 129: 79-84
• 43 Mathé JM, Nomikos GG, Hildebrand BE et al. Prazosin inhibits MK-801-induced hyperlocomotion and dopamine release in the nucleus accumbens. Eur J Pharmacol 1996; 309: 1-11
• 44 Mutlu O, Ulak G, Celikyurt IK et al. Effects of olanzapine, sertindole and clozapine on learning and memory in the Morris water maze test in naive and MK-801-treated mice. Pharmacol Biochem Behavior 2011; 98: 398-404
• 45 Mutlu O, Ulak G, Celikyurt IK et al. Effects of olanzapine, sertindole and clozapine on MK-801 induced visual memory deficits in mice. Pharmacol Biochem Behavior 2011; 99: 557-565