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Mice with reduced NMDA receptor expression display behaviors related to schizophrenia.
A R Mohn1, R R Gainetdinov, M G Caron
1Department of Medicine, University of North Carolina at Chapel Hill 27599. USA.
Cell
|September 11, 1999
Summary
Reduced N-methyl-D-aspartate receptor (NMDAR) activity in mice leads to schizophrenia-like behaviors. Antipsychotic drugs targeting monoaminergic pathways can ameliorate these NMDAR-related behavioral deficits.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- N-methyl-D-aspartate receptors (NMDARs) are crucial glutamate receptors for neuronal development and function.
- The NMDAR1 (NR1) subunit is essential for NMDAR function.
Purpose of the Study:
- To investigate the behavioral consequences of significantly reduced NMDAR1 (NR1) subunit levels.
- To explore the potential of antipsychotic medications in ameliorating NMDAR-related behavioral phenotypes.
Main Methods:
- Generation of mice with approximately 5% of normal NMDAR1 (NR1) subunit levels.
- Behavioral testing of adult mice, including assessments of motor activity, stereotypy, social interaction, and sexual behavior.
- Administration of haloperidol and clozapine to assess their effects on observed behaviors.
Main Results:
- Mice with reduced NR1 levels survived to adulthood and exhibited increased motor activity and stereotypy.
- These mice displayed deficits in social and sexual interactions, mirroring models of schizophrenia.
- Treatment with haloperidol or clozapine ameliorated the schizophrenic-like behaviors.
Conclusions:
- Reduced NMDA receptor activity is sufficient to induce a schizophrenic-like behavioral phenotype in mice.
- Pharmacological targeting of dopaminergic and serotonergic pathways can effectively modulate NMDAR-mediated behavioral alterations.
- This study supports a model linking NMDAR hypofunction to schizophrenia and highlights potential therapeutic strategies.
