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Updated: Apr 5, 2026
Use of the Open Field Maze to Measure Locomotor and Anxiety-like Behavior in Mice
Published on: February 6, 2015
Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801
Neslihan Pınar1, Kubra Akillioglu, Fatih Sefil
1Faculty of Medicine, Medical Pharmacology, Mustafa Kemal University, Hatay, Turkey. drnesli01@gmail.com.
Abstract:
Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (p<0.05), while the open-field test indicated a decrease in locomotor activity (p<0.01). Despite these reductions, clozapine could not reverse the NMDA receptor blockade. Also, as an atypical antipsychotic agent, clozapine could not reverse impairment in the locomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period.
Insights
Clozapine did not reverse developmental NMDA receptor blockade effects on anxiety and locomotion in mice. This study investigated clozapine
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatry
Background:
- Schizophrenia is often accompanied by anxiety and fear disturbances.
- N-methyl-d-aspartate (NMDA) receptor dysfunction is implicated in schizophrenia.
- Atypical antipsychotics like clozapine are used to manage these symptoms.
Purpose of the Study:
- To evaluate clozapine's efficacy in reversing NMDA receptor blockade-induced behavioral changes.
- To assess the impact of developmental NMDA receptor blockade on anxiety and locomotor function in adult mice.
- To determine if clozapine can restore normal behavior and motor activity following early-life NMDA receptor impairment.
Main Methods:
- Male mice received MK-801 (NMDA receptor antagonist) during postnatal days 7-10.
- Adult mice were administered clozapine (atypical antipsychotic).
- Behavioral tests (elevated plus maze, open-field) assessed anxiety and locomotor activity.
Main Results:
- Developmental NMDA receptor blockade reduced anxiety-related behavior and locomotor activity in adulthood.
- Clozapine administration did not reverse the observed reductions in anxiety or locomotion.
- The study found clozapine ineffective in ameliorating NMDA receptor blockade-induced behavioral deficits.
Conclusions:
- Developmental NMDA receptor blockade leads to persistent alterations in anxiety and locomotion.
- Clozapine is not effective in reversing these specific behavioral impairments.
- Further research is needed to understand NMDA receptor roles in schizophrenia pathophysiology and treatment.
