Transient N-methyl-D-aspartate receptor blockade in early development causes lasting cognitive deficits relevant to schizophrenia

Biological Psychiatry
Mark R Stefani, Bita Moghaddam

Abstract

Aberrant N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic transmission has been implicated in schizophrenia. We studied whether transient inhibition of NMDA receptor activity during early postnatal development would produce a behavioral phenotype resembling that of individuals who are susceptible to develop schizophrenia. Rat pups were given injections of the NMDA channel blocker MK801 on postnatal days 7 through 10. This period is akin to the prenatal second trimester of primate development. Cognitive function was tested in adulthood. Treatment with MK801 impaired cognitive flexibility and working memory. The impairment in cognitive flexibility was due to increased perseverative behavior. Treatment did not affect locomotor activity or recognition memory. These results suggest that a brief disruption of NMDA receptors during a sensitive period of cortical development is sufficient to produce selective cognitive deficits that are relevant to schizophrenia.

References

Oct 1, 1991·The American Journal of Psychiatry·D C Javitt, S R Zukin
May 1, 1989·Physiology & Behavior·L F Campbell, K S Bedi
Jul 1, 1987·Archives of General Psychiatry·D R Weinberger
Feb 1, 1993·The American Journal of Psychiatry·R B RosseS I Deutsch
Jan 28, 1998·Critical Reviews in Neurobiology·C A Tamminga
Mar 10, 2000·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Ratna Sircar
Aug 3, 2001·Neuroscience·B ClancyB L Finlay
Jun 14, 2002·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·B K LipskaBita Moghaddam
Dec 14, 2002·Brain Research. Developmental Brain Research·Laura M RitterJames H Meador-Woodruff
Apr 25, 2003·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Ratna Sircar
Jun 5, 2003·Lancet·Maria Karayiorgou, Joseph A Gogos
Aug 23, 2003·Behavioral Neuroscience·Mark R StefaniBita Moghaddam
Sep 27, 2003·The European Journal of Neuroscience·Laura Wiseman HarrisPaul J Harrison

Citations

Apr 17, 2009·Psychopharmacology·Takashi UeharaMasayoshi Kurachi
Oct 21, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Lucila KargiemanPau Celada
Sep 21, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Cheng Z Wang, Kenneth M Johnson
Jan 22, 2009·Schizophrenia Bulletin·Klaas E StephanChris D Frith
Aug 25, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mark R Stefani, Bita Moghaddam
Jan 4, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Daniel R ThomasesKuei Y Tseng
Nov 9, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hongbo HeJeffrey D Erickson
Feb 24, 2016·Neurotoxicology and Teratology·Bonnie L RobinsonJyotshna Kanungo
Jan 15, 2016·Nature Reviews. Neuroscience·Giles E Hardingham, Kim Q Do
Jan 23, 2013·Neurobiology of Disease·Saurav SeshadriAkira Sawa
Oct 4, 2011·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Teresa Marie du BoisXu-Feng Huang
Apr 6, 2011·Pharmacology, Biochemistry, and Behavior·Chieh-Hsin LinGuochuan E Tsai
Mar 5, 2011·Progress in Neuro-psychopharmacology & Biological Psychiatry·Amy E GeddesKelly Anne Newell
Mar 6, 2016·Neuropharmacology·Francesca M Notarangelo, Ana Pocivavsek
Oct 28, 2009·Progress in Neurobiology·Urs Meyer, Joram Feldon
Jun 16, 2009·Neuropharmacology·M Margarita Behrens, Terrence J Sejnowski
May 5, 2009·Pharmacology, Biochemistry, and Behavior·Leon G ColemanFulton T Crews
May 12, 2009·Behavioural Brain Research·Yong LiuJingping Zhao
Jan 20, 2009·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Teresa Marie du BoisXu-Feng Huang
Oct 23, 2008·Progress in Neuro-psychopharmacology & Biological Psychiatry·Teresa Marie du BoisXu-Feng Huang
May 13, 2008·Neuroscience and Biobehavioral Reviews·Vera Bubeníková-ValesováCyril Höschl
Apr 1, 2011·British Journal of Pharmacology·C A JonesK C F Fone
Apr 25, 2013·CNS Neuroscience & Therapeutics·Bernat KocsisMihaly Hajos
Jul 29, 2015·Developmental Neurobiology·Vládia Célia Moreira BorellaDanielle Macêdo
Oct 4, 2006·Brain Research Reviews·Teresa Marie du Bois, Xu-Feng Huang
Apr 9, 2015·Biological Psychiatry·Benjamin R Pittman-PollettaNancy J Kopell
Jun 28, 2012·Progress in Neuro-psychopharmacology & Biological Psychiatry·Tihomir StojkovićNataša D Petronijević
Jan 17, 2009·Physiology & Behavior·Amber L AdamsCatherine L Ryan
Feb 6, 2015·Therapeutic Advances in Psychopharmacology·Hannah SteedsJames M Stone
Dec 21, 2019·Behavioural Pharmacology·Pushparaj GawaiRajesh R Ugale
Jun 21, 2018·Frontiers in Molecular Neuroscience·Megan M WickensLisa A Briand

Related Concepts

Behavior, Animal
Overinclusion
Discrimination (Process of Differentiation)
Curiosity
Locomotion
Immediate Recall
Memory for Designs Test
Psychomotor Performance
Schizophrenia
N-Methyl-D-Aspartate Receptors

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