Mice with reduced NMDA receptor expression display behaviors related to schizophrenia.

Published

Journal Article

N-methyl-D-aspartate receptors (NMDARs) represent a subclass of glutamate receptors that play a critical role in neuronal development and physiology. We report here the generation of mice expressing only 5% of normal levels of the essential NMDAR1 (NR1) subunit. Unlike NR1 null mice, these mice survive to adulthood and display behavioral abnormalities, including increased motor activity and stereotypy and deficits in social and sexual interactions. These behavioral alterations are similar to those observed in pharmacologically induced animal models of schizophrenia and can be ameliorated by treatment with haloperidol or clozapine, antipsychotic drugs that antagonize dopaminergic and serotonergic receptors. These findings support a model in which reduced NMDA receptor activity results in schizophrenic-like behavior and reveals how pharmacological manipulation of monoaminergic pathways can affect this phenotype.

Full Text

Duke Authors

Cited Authors

  • Mohn, AR; Gainetdinov, RR; Caron, MG; Koller, BH

Published Date

  • August 1999

Published In

Volume / Issue

  • 98 / 4

Start / End Page

  • 427 - 436

PubMed ID

  • 10481908

Pubmed Central ID

  • 10481908

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/s0092-8674(00)81972-8

Language

  • eng