Innovative Use of IntelliCage to Study Spontaneous Behaviors in Schizophrenia Mouse Models

Schizophrenia is a complex mental disorder characterized by symptoms such as hallucinations, delusions, social withdrawal, cognitive impairments, and disorganized thinking. Despite extensive research, the precise biological mechanisms of the disorder remain unclear, and current animal models often rely on external stimuli or human handling to assess behavioral changes.

A recent advancement in preclinical research involves the use of the IntelliCage system—a fully automated, naturalistic cage environment equipped with RFID technology to monitor individual mice behaviors over extended periods without human interference. Researchers led by Assistant Professor Hisayoshi Kubota from Fujita Health University utilized this platform to evaluate spontaneous behavioral patterns in a mouse model of schizophrenia.

The IntelliCage allows each mouse to be tagged with a unique microchip, enabling personalized tracking of activities such as corner visits, nose pokes, and licking behaviors. These features facilitate the assessment of solitary and group behaviors relevant to psychiatric symptoms. The study, published in the
International Journal of Molecular Sciences on May 28, 2025, highlights how this system can provide ecologically valid insights into disease phenotypes.

The team induced schizophrenia-like behaviors in mice using MK-801, an NMDA receptor antagonist known to produce symptoms mirroring human schizophrenia, including hyperactivity, social deficits, and impaired cognition. Using IntelliCage, they observed that MK-801-treated mice initially showed increased corner visits, indicating transient hyperactivity and exploratory behavior. Interestingly, the treated mice maintained a preference for sugar solutions, suggesting reward sensitivity was intact. However, they exhibited decreased water-seeking behavior after prolonged deprivation, signifying possible deficits in reward-seeking or motivation.

Cognitive assessments further revealed that while MK-801 mice could learn reward locations, they struggled to adapt when reward patterns changed. Their delayed responses and prolonged learning curves demonstrated impairments in cognitive flexibility, a core feature of schizophrenia.

This research underscores the value of noninvasive, long-term behavioral analysis in psychiatric models. The IntelliCage system can help unravel the molecular and circuit mechanisms underlying schizophrenia and expedite therapeutic discovery. Dr. Kubota emphasizes that adopting this technology widely could standardize behavioral assessments and improve translational research efforts, ultimately leading to better treatments for patients.

Overall, combining automated environmental monitoring with pharmacological models offers promising avenues for understanding and tackling schizophrenia’s multifaceted nature.