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

Mark Renato Stefani; Bita Moghaddam

doi:10.1016/j.biopsych.2004.11.031

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

Mark Renato Stefani, Bita Moghaddam

Research output: Contribution to journal › Article › peer-review

138 Scopus citations

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original language	English (US)
Pages (from-to)	433-436
Number of pages	4
Journal	Biological Psychiatry
Volume	57
Issue number	4
DOIs	https://doi.org/10.1016/j.biopsych.2004.11.031
State	Published - Feb 15 2005
Externally published	Yes

Keywords

Glutamate
MK801
Memory
Prefrontal
Set-shift
Spontaneous alternation

ASJC Scopus subject areas

Biological Psychiatry

Access to Document

10.1016/j.biopsych.2004.11.031

Cite this

@article{b6de5756442c418b9b9d0a1ef81b0c40,

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

abstract = "Background: 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. Methods: 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. Results: 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. Conclusions: 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.",

keywords = "Glutamate, MK801, Memory, Prefrontal, Set-shift, Spontaneous alternation",

author = "Stefani, {Mark Renato} and Bita Moghaddam",

note = "Funding Information: This work was supported by the National Institute of Mental Health (R37MH48404, R21MH65026, K02MH01616). ",

year = "2005",

month = feb,

day = "15",

doi = "10.1016/j.biopsych.2004.11.031",

language = "English (US)",

volume = "57",

pages = "433--436",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier USA",

number = "4",

}

TY - JOUR

T1 - Transient N-methyl-D-aspartate receptor blockade in early development causes lasting cognitive deficits relevant to schizophrenia

AU - Stefani, Mark Renato

AU - Moghaddam, Bita

N1 - Funding Information: This work was supported by the National Institute of Mental Health (R37MH48404, R21MH65026, K02MH01616).

PY - 2005/2/15

Y1 - 2005/2/15

N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

KW - Glutamate

KW - MK801

KW - Memory

KW - Prefrontal

KW - Set-shift

KW - Spontaneous alternation

UR - http://www.scopus.com/inward/record.url?scp=13444306480&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13444306480&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2004.11.031

DO - 10.1016/j.biopsych.2004.11.031

M3 - Article

C2 - 15705361

AN - SCOPUS:13444306480

SN - 0006-3223

VL - 57

SP - 433

EP - 436

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this