Download PDF
Arzneimittelforschung 2012; 62(01): 4-8
DOI: 10.1055/s-0031-1291360
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

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

O. Mutlu
1   Kocaeli University Medical Faculty, Pharmacology Department, Kocaeli, Turkey
,
I. K. Celikyurt
1   Kocaeli University Medical Faculty, Pharmacology Department, Kocaeli, Turkey
,
G. Ulak
1   Kocaeli University Medical Faculty, Pharmacology Department, Kocaeli, Turkey
,
P. Tanyeri
1   Kocaeli University Medical Faculty, Pharmacology Department, Kocaeli, Turkey
,
F. Y. Akar
1   Kocaeli University Medical Faculty, Pharmacology Department, Kocaeli, Turkey
,
F. Erden
1   Kocaeli University Medical Faculty, Pharmacology Department, Kocaeli, Turkey
› Author Affiliations
Further Information

Publication History

received 15 September 2011

accepted 17 October 2011

Publication Date:
10 January 2012 (online)

   Permissions and Reprints

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
    Google Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 5 Mortimer AM. Cognitive function in schizophrenia – do neuroleptics make a difference?. Pharmacol Biochem Behav 1997; 56: 789-795
    CrossrefPubMedGoogle Scholar
  • 6 Cleghorn JM, Kaplan RD, Szechtman B et al. Neuroleptic drug effects on cognitive function in schizophrenia. Schizophr Res 1990; 3: 211-219
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 8 Kane JM, Tamminga CA. Sertindole (serdolect): preclinical and clinical findings of a new atypical antipsychotic. Exp Opin Invest Drugs 1997; 6: 1729-1741
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 11 Harvey PD, Kefe RS. Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry 2001; 158: 176-184
    Google Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 13 Meltzer HY, McGurk SR. The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull 1999; 25: 233-255
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 18 Skarsfeldt T. Differential effect of antipsychotics on place navigation of rats in the Morris water maze. Psychopharmacology 1996; 124: 126-133
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 26 Bymaster F, Perry KW, Nelson DL et al. Olanzapine: a basic science update. Br J Psychiatry Suppl 1999; 37: 36-40
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 28 Stephenson CM, Pilowsky LS. Psychological of olanzapine. A review. Br J Psychiatry 1999; 38: 52-58
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 39 Lipska BK, Weinberger DR. To model a psychiatric disorder in animals: schizophrenia as a reality test. Neuropsychopharmacology 2000; 23: 223-239
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar