The mirror preference test: A reverse translational approach to study anomalous subjective experience in rats

Significant advancements have been made in the treatment of psychotic disorders, yet current pharmacotherapy remains inadequate. Symptoms related to the misinterpretation of reality are crucial for diagnosis but pose challenges for preclinical research. In humans, a Mirror-Gazing test is used to exa...

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Main Authors: Daria Chestnykh, Liubov S. Kalinichenko, Stephan von Hörsten, Johannes Kornhuber, Christian P. Müller
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S0361923025000590
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author Daria Chestnykh
Liubov S. Kalinichenko
Stephan von Hörsten
Johannes Kornhuber
Christian P. Müller
author_facet Daria Chestnykh
Liubov S. Kalinichenko
Stephan von Hörsten
Johannes Kornhuber
Christian P. Müller
author_sort Daria Chestnykh
collection DOAJ
description Significant advancements have been made in the treatment of psychotic disorders, yet current pharmacotherapy remains inadequate. Symptoms related to the misinterpretation of reality are crucial for diagnosis but pose challenges for preclinical research. In humans, a Mirror-Gazing test is used to examine abnormal self-experience and to predict the risk of schizophrenia. To address this, we developed a task to evaluate anomalous subjective experiences in rats using a Mirror-Preference test. Here we demonstrate that naive rats show a preference for a mirror chamber, which was followed by significant habituation over a series of trials. In subsequent tests, we utilized dimmed lighting and net-covered mirrors to induce incomplete mirror images. Acute stimulation with amphetamine (AMPH, 3 mg/kg, i.p.) further increased the preference for the mirror. In a model of psychosis induced by chronic AMPH administration, rats showed fewer and shorter interactions with the mirror but maintained their preference for the chamber where psychotic-like animals were given additional AMPH stimulation (1.5 mg/kg, i.p.) before testing. Here, a surprising reversal in chamber preference was observed, along with decreased frequency and duration of mirror contact, suggesting mirror avoidance. The AMPH-presensitized rats also exhibited hyperlocomotion and elevated anxiety, indicative of psychotic-like behaviour. Although self-recognition in rodents is debatable, recent studies suggest they can discriminate mirror images. We propose that limited visual perception that meets brain monoamine sensitization may trigger visual illusions as part of a psychotic-like state in rats. This novel approach can be utilized to test intervention strategies for psychosis in rats.
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spelling doaj-art-c4df10b3de8e4f7f973c4715db1194242025-02-08T04:59:28ZengElsevierBrain Research Bulletin1873-27472025-03-01222111247The mirror preference test: A reverse translational approach to study anomalous subjective experience in ratsDaria Chestnykh0Liubov S. Kalinichenko1Stephan von Hörsten2Johannes Kornhuber3Christian P. Müller4Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, GermanyDepartment of Experimental Therapy, Preclinical Experimental Center, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany; Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Correspondence to: Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, Erlangen, Germany.Significant advancements have been made in the treatment of psychotic disorders, yet current pharmacotherapy remains inadequate. Symptoms related to the misinterpretation of reality are crucial for diagnosis but pose challenges for preclinical research. In humans, a Mirror-Gazing test is used to examine abnormal self-experience and to predict the risk of schizophrenia. To address this, we developed a task to evaluate anomalous subjective experiences in rats using a Mirror-Preference test. Here we demonstrate that naive rats show a preference for a mirror chamber, which was followed by significant habituation over a series of trials. In subsequent tests, we utilized dimmed lighting and net-covered mirrors to induce incomplete mirror images. Acute stimulation with amphetamine (AMPH, 3 mg/kg, i.p.) further increased the preference for the mirror. In a model of psychosis induced by chronic AMPH administration, rats showed fewer and shorter interactions with the mirror but maintained their preference for the chamber where psychotic-like animals were given additional AMPH stimulation (1.5 mg/kg, i.p.) before testing. Here, a surprising reversal in chamber preference was observed, along with decreased frequency and duration of mirror contact, suggesting mirror avoidance. The AMPH-presensitized rats also exhibited hyperlocomotion and elevated anxiety, indicative of psychotic-like behaviour. Although self-recognition in rodents is debatable, recent studies suggest they can discriminate mirror images. We propose that limited visual perception that meets brain monoamine sensitization may trigger visual illusions as part of a psychotic-like state in rats. This novel approach can be utilized to test intervention strategies for psychosis in rats.http://www.sciencedirect.com/science/article/pii/S0361923025000590MirrorAmphetamineSchizophreniaPsychosisRatsPlace preference
spellingShingle Daria Chestnykh
Liubov S. Kalinichenko
Stephan von Hörsten
Johannes Kornhuber
Christian P. Müller
The mirror preference test: A reverse translational approach to study anomalous subjective experience in rats
Brain Research Bulletin
Mirror
Amphetamine
Schizophrenia
Psychosis
Rats
Place preference
title The mirror preference test: A reverse translational approach to study anomalous subjective experience in rats
title_full The mirror preference test: A reverse translational approach to study anomalous subjective experience in rats
title_fullStr The mirror preference test: A reverse translational approach to study anomalous subjective experience in rats
title_full_unstemmed The mirror preference test: A reverse translational approach to study anomalous subjective experience in rats
title_short The mirror preference test: A reverse translational approach to study anomalous subjective experience in rats
title_sort mirror preference test a reverse translational approach to study anomalous subjective experience in rats
topic Mirror
Amphetamine
Schizophrenia
Psychosis
Rats
Place preference
url http://www.sciencedirect.com/science/article/pii/S0361923025000590
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