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Publication : Dissociation between sickness behavior and emotionality during lipopolysaccharide challenge in lymphocyte deficient Rag2(-/-) mice.

First Author  Clark SM Year  2015
Journal  Behav Brain Res Volume  278
Pages  74-82 PubMed ID  25257108
Mgi Jnum  J:216973 Mgi Id  MGI:5610093
Doi  10.1016/j.bbr.2014.09.030 Citation  Clark SM, et al. (2014) Dissociation between sickness behavior and emotionality during lipopolysaccharide challenge in lymphocyte deficient Rag2 mice. Behav Brain Res 278C:74-82
abstractText  Inflammatory diseases are highly associated with affective disorders including depression and anxiety. While the role of the innate immune system on emotionality has been extensively studied, the role of adaptive immunity is less understood. Considering that chronic inflammatory conditions are mediated largely by maladaptive lymphocyte function, the role of these cells on brain function and behavior during inflammation warrants investigation. In the present study we employed mice deficient in lymphocyte function and studied behavioral and inflammatory responses during challenge with bacterial lipopolysaccharides (LPS). Rag2-/- mice lacking mature lymphocytes were susceptible to death under sub-septic (5mg/kg) doses of LPS and survived only to moderate (1mg/kg) doses of LPS. Under these conditions, they displayed attenuated TNF-alpha responses and behavioral symptoms of sickness when compared with immunocompetent mice. Nevertheless, Rag2-/- mice had protracted motivational impairments after recovery from sickness suggesting a specific function for lymphocytes on the re-establishment of motivational states after activation of the innate immune system. The behavioral impairments in Rag2-/- mice were paralleled by an elevation in plasma corticosterone after behavioral tests. These results provide evidence that the absence of adaptive immunity may be associated with emotional deficits during inflammation and suggest that depressive states associated with medical illness may be mediated in part by impaired lymphocyte responses.
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