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Proclivity to self-injurious behavior in MRL-lpr mice: implications for autoimmunity-induced damage in the dopaminergic system

Molecular Psychiatry volume 13, pages 1043–1053 (2008)Cite this article

Abstract

Systemic lupus erythematosus is frequently accompanied by psychiatric manifestations of unknown origin. Although damage of central neurons had been documented, little is known about neurotransmitter systems affected by the autoimmune/inflammatory process. Recent studies on lupus-prone MRL-lpr mice point to imbalanced dopamine function and neurodegeneration in dopamine-rich brain regions. We follow up on anecdotal observations of singly housed mice developing chest wounds. Compulsive grooming and/or skin biting accounted for open lesions, lending itself to the operational term ‘self-injurious behavior’ (SIB). Low incidence of spontaneous SIB increased significantly after repeated injections of dopamine-2/3 receptor (D2/D3R) agonist quinpirole (QNP). To further probe the dopaminergic circuitry and examine whether SIB is associated with development of lupus-like disease, we compared behavioral responses among cohorts that differed in the immune status. Two-week treatment with QNP (intraperitoneal, 0.5 mg kg−1 body weight per day) induced SIB in 60% of diseased MRL-lpr mice, and exacerbated their splenomegaly. Although increased grooming and stereotypy were observed in less symptomatic MRL+/+ controls, only one mouse (10%) developed SIB. Similarly, SIB was not seen in young, asymptomatic groups despite dissimilar ambulatory responses to QNP. In situ hybridization revealed treatment-independent upregulation of D2R mRNA in substantia nigra of diseased MRL-lpr mice. The above results suggest that development of systemic autoimmunity alters sensitivity of the dopaminergic system and renders MRL-lpr mice prone to SIB. Although pathogenic factors were not examined, we hypothesize that immune and endocrine mechanisms jointly contribute to early neuronal damage, which underlies behavioral deficiency in the adulthood.

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Acknowledgements

We thank Henry Szechtman for his constructive comments on our article. This work was supported by funds from the National Institute of Health (1R21 AR49163-01) and Canadian Institutes of Health Research (grant MOP 38065). B Sakic is a recipient of the Father Sean O’Sullivan Research Centre (FSORC) career development award. S Chun is a recipient of the NSERC fellowship.

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  1. Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada

    S Chun, R McEvilly, J A Foster & B Sakic

  2. The Brain Body Institute, St Joseph's Healthcare, Hamilton, ON, Canada

    J A Foster & B Sakic

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Correspondence to B Sakic.

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Chun, S., McEvilly, R., Foster, J. et al. Proclivity to self-injurious behavior in MRL-lpr mice: implications for autoimmunity-induced damage in the dopaminergic system. Mol Psychiatry 13, 1043–1053 (2008). https://doi.org/10.1038/sj.mp.4002078

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