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Rationale <p>An abnormal sense of agency (SoA) is one of the core symptoms of schizophrenia. Patients with predominantly positive symptoms exhibit its enhancement, misattributing the cause of external events that occur independently of their behaviour to themselves. However, preclinical animal model studies on this critical aspect are lacking, which prevents further elucidation of its neurobiological and molecular underpinnings.</p> Objectives <p>We developed a conditional discrimination task for mice that required the animals to report their subjective judgement of instrumental action‒outcome contingency and used this task to examine whether ketamine, an <i>N</i>-methyl-D-aspartate-receptor antagonist used to model the psychotic symptoms of schizophrenia, disrupted contingency judgement.</p> Methods <p>C57BL/6J mice were trained on a conditional discrimination task in which a target event occurred either contingently or noncontingently on the animal’s voluntary response. The mice were food-reinforced to press one lever if the event was caused by their own response and another lever if the event occurred independently of their behaviour. After acquisition, half of the mice were injected with 16&#xa0;mg/kg ketamine before each test session, while the others received saline.</p> Results <p>Ketamine increased false alarm responses (i.e., incorrect self-attribution judgements), specifically when the target event occurred noncontingently but with a delay of 0.3–0.5&#xa0;s after a response. These results indicate that the ketamine-injected mice were prone to misattribute the cause of an external event to themselves.</p> Conclusions <p>This study provides a behavioural paradigm for studying the mouse-analogue of SoA and further demonstrates the enhancement of SoA in the acute ketamine model of schizophrenia.</p>

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Impaired contingency judgement in mice under ketamine: an implication for an altered sense of agency in schizophrenia

  • 期刊论文

  • 发表日期：

    2025年12月19日

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  • Riria Suzuki,
  • Yutaka Kosaki

摘要

Rationale

An abnormal sense of agency (SoA) is one of the core symptoms of schizophrenia. Patients with predominantly positive symptoms exhibit its enhancement, misattributing the cause of external events that occur independently of their behaviour to themselves. However, preclinical animal model studies on this critical aspect are lacking, which prevents further elucidation of its neurobiological and molecular underpinnings.

Objectives

We developed a conditional discrimination task for mice that required the animals to report their subjective judgement of instrumental action‒outcome contingency and used this task to examine whether ketamine, an N-methyl-D-aspartate-receptor antagonist used to model the psychotic symptoms of schizophrenia, disrupted contingency judgement.

Methods

C57BL/6J mice were trained on a conditional discrimination task in which a target event occurred either contingently or noncontingently on the animal’s voluntary response. The mice were food-reinforced to press one lever if the event was caused by their own response and another lever if the event occurred independently of their behaviour. After acquisition, half of the mice were injected with 16 mg/kg ketamine before each test session, while the others received saline.

Results

Ketamine increased false alarm responses (i.e., incorrect self-attribution judgements), specifically when the target event occurred noncontingently but with a delay of 0.3–0.5 s after a response. These results indicate that the ketamine-injected mice were prone to misattribute the cause of an external event to themselves.

Conclusions

This study provides a behavioural paradigm for studying the mouse-analogue of SoA and further demonstrates the enhancement of SoA in the acute ketamine model of schizophrenia.