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Enhanced Aggressive Behaviour in a Mouse Model of Depression

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Abstract

Depression is one of the most common chronic mental disorders, which is a leading cause of morbidity and mortality in patients. Depression often leads to offensive and defensive behaviours but the underlying mechanisms are not known. We propose that the aggressive behaviours in depression can be modelled in animal experiments. In this study, we successfully established a mouse model of depression using the chronic unpredictable mild stress (CUMS) paradigm and detected aggressive and social dominance behaviours in rodents by resident/intruder test and social dominance tube test (SDTT), respectively. The CUMS-exposed mice showed increased defensive, offensive and aggressive behaviours in the resident–intruder test. In the SDTT, these mice showed enhanced social dominance. These alterations were associated with reduced MAP-2 expression in the hippocampus while no difference in β-tubulin expression was detected. In addition, the treatment of anti-depressant fluoxetine reversed the aggressive behaviours without reducing the social dominance behaviour induced by CUMS. However, fluoxetine did effectively reverted the changes in MAP-2 expression in the hippocampus. In addition, the nonspecific tricyclic antipsychotic drug, clozapine, reversed all symptoms of CUMS-exposed mice including aggressive tendencies, impulsive violence, social dominance behaviour and MAP-2 expression in the hippocampus. The results suggests that social maladjustment such as competition and social dominance are likely related to the dopaminergic system rather than the serotonergic system and the hippocampal dendritic structure protein MAP-2. Thus, dominance can be separated from aggression. This study shows that aggression/hostility and social hierarchy/dominance are increased in the CUMS-exposed mice and thus provide an excellent model for further study in the diagnosis and the treatment of depression-associated aggression.

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Acknowledgments

The authors wish to thank Mr. Mark Vyner-Smith for proof reading the manuscript. The animal experimental work was done in Kunming Medical University (KMU). X. F. Z. is a visiting professor of KMU. F. H. Zhou was supported by NHMRC overseas bio-medical training fellowship.

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Authors and Affiliations

  1. Department of Pathology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China

    C. R. Yang, X. F. Wang & H. Y. Zheng

  2. The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, Yunnan, People’s Republic of China

    C. R. Yang, Y. Y. Bai, C. S. Ruan & X. F. Zhou

  3. School of Pharmacology and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, SA, Australia

    C. S. Ruan, H. F. Zhou & X. F. Zhou

  4. Department of Psychiatry, Liupanshui Third People’s Hospital, Guizhou, People’s Republic of China

    Y. Y. Bai

  5. Mental Health Service, Northern Adelaide Local Health Network, Adelaide, SA, Australia

    D. Liu

  6. Department of Pathology, Kunming Medical University, Kunming, Yunnan, People’s Republic of China

    L. J. Shen

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  1. C. R. Yang
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  2. Y. Y. Bai
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  4. H. F. Zhou
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  9. X. F. Zhou
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Correspondence to H. Y. Zheng or X. F. Zhou.

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Yang, C.R., Bai, Y.Y., Ruan, C.S. et al. Enhanced Aggressive Behaviour in a Mouse Model of Depression. Neurotox Res 27, 129–142 (2015). https://doi.org/10.1007/s12640-014-9498-4

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  • DOI: https://doi.org/10.1007/s12640-014-9498-4

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