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

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.

Pubmed ID: 10481908


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



Publication Data

August 20, 1999

Associated Grants

  • Agency: NINDS NIH HHS, Id: NS19576
  • Agency: NIGMS NIH HHS, Id: T32GM07092

Mesh Terms

  • Animals
  • Antipsychotic Agents
  • Antisocial Personality Disorder
  • Behavior, Animal
  • Calcium Signaling
  • Clozapine
  • Disease Models, Animal
  • Dizocilpine Maleate
  • Dopamine Antagonists
  • Excitatory Amino Acid Antagonists
  • Female
  • Glutamic Acid
  • Haloperidol
  • Male
  • Mice
  • Mice, Knockout
  • Motor Activity
  • Phencyclidine
  • Receptors, N-Methyl-D-Aspartate
  • Schizophrenic Psychology
  • Serotonin Antagonists
  • Sexual Behavior, Animal
  • Social Behavior
  • Stereotyped Behavior