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Persisting cognitive deficits induced by low-dose, subchronic treatment with MK-801 in adolescent rats
Ji-Tao Li1, Yun-Ai Su, Chun-Mei Guo
1Institute of Mental Health, Peking Univeristy, Beijing, China.
Abstract:
Cognitive impairments have been proposed as a core feature of schizophrenia. Studies have shown that chronic or subchronic treatment with N-methyl-d-aspartate (NMDA) antagonists could induce cognitive deficits that resemble the symptoms of schizophrenia, yet few studies have investigated the effects of repeated NMDA blockade during adolescence on cognition. In the current study, adolescent, male rats were treated with an intraperitoneal injection of MK-801 (0.05, 0.1, and 0.2mg/kg) once daily for 14days. They were then tested 24h and 14days after drug cessation, respectively, in a series of behavioural tasks, including the object recognition task, the object-in-context recognition task and the working memory task of the Morris water maze (MWM). Results showed that object-in-context recognition and spatial working memory in the MWM were significantly impaired by repeated MK-801 treatment when animals were tested 24h after drug cessation, but object recognition was left intact. In particular, such deficits were observed 14days after drug cessation in the 0.2mg/kg group. The cognition-impairing effect of MK-801 could not be attributed to malnutrition or alterations in motor functions. Taken together, this study may provide support for establishing an animal model of cognitive deficits of schizophrenia based on low-dose, repeated treatment of MK-801 during adolescence.
Insights
Adolescent rats repeatedly given MK-801 showed impaired cognition, particularly object-in-context recognition and working memory. These deficits persisted even after drug cessation, suggesting a potential animal model for schizophrenia-related cognitive dysfunction.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Cognitive impairments are a core feature of schizophrenia.
- N-methyl-d-aspartate (NMDA) antagonists can induce schizophrenia-like cognitive deficits.
- Effects of adolescent NMDA receptor blockade on cognition are understudied.
Purpose of the Study:
- To investigate the long-term effects of repeated NMDA antagonist (MK-801) treatment during adolescence on cognitive functions in rats.
- To determine if MK-801-induced cognitive deficits resemble those seen in schizophrenia.
- To establish a potential animal model for schizophrenia's cognitive symptoms.
Main Methods:
- Adolescent male rats received daily intraperitoneal injections of MK-801 (0.05, 0.1, 0.2 mg/kg) for 14 days.
- Behavioral testing included object recognition, object-in-context recognition, and Morris water maze (working memory) tasks.
- Cognitive performance was assessed 24 hours and 14 days after the final drug administration.
Main Results:
- Repeated MK-801 treatment significantly impaired object-in-context recognition and spatial working memory 24 hours post-cessation.
- Object recognition memory remained intact.
- Cognitive deficits, particularly in the higher dose group (0.2 mg/kg), persisted 14 days after drug cessation.
- MK-801 effects were not due to malnutrition or motor function changes.
Conclusions:
- Repeated adolescent NMDA receptor blockade with MK-801 induces lasting cognitive deficits in rats.
- These findings support the use of low-dose, repeated MK-801 treatment during adolescence as an animal model for schizophrenia-related cognitive impairments.
- This model may aid in understanding and developing treatments for cognitive dysfunction in schizophrenia.
