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Authors & Affiliations
Daria Chestnykh, Stephan von Hörsten, Johannes Kornhuber, Christian P. Müller
Abstract
Tremendous progress has been made in treating psychotic disorders, although available pharmacotherapy remains insufficient. Symptoms related to reality misinterpretation are key for diagnosis but challenging in preclinical research. In humans, the Mirror-Gazing test has been employed to examine abnormal self-experience and to predict a risk of schizophrenia manifestation. The lack of corresponding animal methods impedes the development of novel drugs for early antipsychotic interventions. We established a task to evaluate anomalous subjective experience in rats using a mirror test. Initially, we showed a mirror chamber preference in naïve rats followed by notable habituation in a series of trials. To trigger visual illusions, we used dimmed light and a net-covered mirror in the subsequent tests. Acute dopamine stimulation by amphetamine (AMPH) enhanced the mirror preference even further. In a model of psychosis induced by chronic AMPH administration, we observed fewer and shorter contacts with a mirror but the maintenance in chamber preference. To mimic the dopamine supersensitivity of schizophrenic patients, psychotic-like animals were additionally stimulated with AMPH before the test. Surprisingly, this resulted in reversed chamber preference and decreased frequency and duration of contacts, suggesting mirror avoidance. AMPH-presensitized rats also demonstrated hyperlocomotion and elevated anxiety, indicating psychotic-like behaviour. Albeit self-recognition in rodents is questionable, recent findings argue they can discriminate mirror images. We suggest, that limited visual perception and enhanced dopamine levels might trigger mirror illusions compelling psychotic-like rats to avoid it. This new approach might be applied for the improvement of early intervention strategies during a prodromal phase of psychosis.