Abnormal Motor Activity and Thermoregulation in a Schizophrenia Rat Model for Translational Science.

Gyongyi Horvath,Zita Petrovszki,Gabriella Kekesi,Gyorgy Benedek,Sheila Fleming

doi:10.1371/journal.pone.0143751

Gyongyi Horvath, Zita Petrovszki + Show 3 more

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https://doi.org/10.1371/journal.pone.0143751

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Journal: PloS one	Publication Date: Dec 2, 2015
Citations: 22	License type: CC BY 4.0

Affiliation: University of Szeged

Abstract

BackgroundSchizophrenia is accompanied by altered motor activity and abnormal thermoregulation; therefore, the presence of these symptoms can enhance the face validity of a schizophrenia animal model. The goal was to characterize these parameters in freely moving condition of a new substrain of rats showing several schizophrenia-related alterations.MethodsMale Wistar rats were used: the new substrain housed individually (for four weeks) and treated subchronically with ketamine, and naive animals without any manipulations. Adult animals were implanted with E-Mitter transponders intraabdominally to record body temperature and locomotor activity continuously. The circadian rhythm of these parameters and the acute effects of changes in light conditions were analyzed under undisturbed circumstances, and the effects of different interventions (handling, bed changing or intraperitoneal vehicle injection) were also determined.ResultsDecreased motor activity with fragmented pattern was observed in the new substrain. However, these animals had higher body temperature during the active phase, and they showed wider range of its alterations, too. The changes in light conditions and different interventions produced blunted hyperactivity and altered body temperature responses in the new substrain. Poincaré plot analysis of body temperature revealed enhanced short- and long-term variabilities during the active phase compared to the inactive phase in both groups. Furthermore, the new substrain showed increased short- and long-term variabilities with lower degree of asymmetry suggesting autonomic dysregulation.ConclusionsIn summary, the new substrain with schizophrenia-related phenomena showed disturbed motor activity and thermoregulation suggesting that these objectively determined parameters can be biomarkers in translational research.

Highlights

Animal models are important tools for understanding pathological mechanisms, but they are necessary for testing hypotheses that cannot be addressed in human studies and for developing and preclinical testing of new treatments [1]
Decreased motor activity with fragmented pattern was observed in the new substrain
Poincaré plot analysis of body temperature revealed enhanced short- and long-term variabilities during the active phase compared to the inactive phase in both groups

Summary

Introduction

Animal models are important tools for understanding pathological mechanisms, but they are necessary for testing hypotheses that cannot be addressed in human studies and for developing and preclinical testing of new treatments [1]. A complex animal model has been developed by selective breeding based on behavioral alterations after combined subchronic ketamine treatment (NMDA-receptor antagonist) and postweaning social isolation [2,3]. These animals showed several signs of schizophrenia, i.e., disturbed pain sensitivity, sensory gating, stereotypic behaviors and cognitive functions suggesting that they might be a more reliable model of schizophrenia than naive animals with isolation and ketamine treatment or the new substrain without any treatment. The goal was to characterize these parameters in freely moving condition of a new substrain of rats showing several schizophrenia-related alterations.

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