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The postweaning social isolation in C57BL/6 mice: preferential vulnerability in the male sex

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Abstract

Introduction

Social deprivation during early life can severely affect mental health later in adulthood, leading to the development of behavioural traits associated with several major psychiatric disorders including schizophrenia. This has led to the application of social isolation in laboratory animals to model the impact of environmental factors on the aetiopathology of schizophrenia. However, controversy exists over the precise behavioural profile and the robustness of some of the reported effects of social isolation rearing.

Materials and methods

Here, we evaluated the efficacy of postweaning social isolation to induce schizophrenia-related behavioural deficits in C57BL/6 mice of both sexes.

Results

The effects of social isolation clearly differed between sexes: isolated male but not female mice exhibited multiple habituation deficits and enhanced locomotor reaction to amphetamine.

Discussion

The preferential vulnerability in the male sex corresponds well with the earlier disease onset and poorer prognosis in male relative to female schizophrenic patients. In contrast, we observed no evidence for a disruption of sensorimotor gating in the prepulse inhibition paradigm despite the efficacy of social isolation to alter startle reactivity. With both success and failure in the induction of schizophrenia-related endophenotypes, the present study thus provides important characterizations and qualifications to the application of the social isolation model in mice.

Conclusions

We conclude that social isolation in mice represents a valuable tool for the examination of candidate genes within the context of the “two-hit” hypothesis of the aetiological processes in schizophrenia.

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Acknowledgments

The present study was supported by a Swiss National Science Foundation (SNF) 3100A0-100309/1 grant awarded to JF, with additional support by the Swiss Federal Institute of Technology, and the National Centre for Competence in Research (NCCR): Neural Plasticity and Repair. The authors also thank Peter Schmid for his technical assistance, the animal technicians for their caring of the animals, and Dr. Frank Bootz for his veterinary expertise and supervision.

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Correspondence to Benjamin K. Yee.

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Pietropaolo, S., Singer, P., Feldon, J. et al. The postweaning social isolation in C57BL/6 mice: preferential vulnerability in the male sex. Psychopharmacology 197, 613–628 (2008). https://doi.org/10.1007/s00213-008-1081-3

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