title: Dissociation between sickness behavior and emotionality during lipopolysaccharide challenge in lymphocyte deficient Rag2(-/-) mice.
abstract: 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 (5 mg/kg) doses of LPS and survived only to moderate (1 mg/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.
authors.affiliation: Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, United States; Research and Development Service, Department of Veterans Affairs, VA Maryland Health Care System, Baltimore, MD, United States.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Clark
authors.affiliation: Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, United States.
authors.forename: Kerry C
authors.initials: KC
authors.lastname: Michael
authors.affiliation: Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Klaus
authors.affiliation: Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, United States.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Mert
authors.affiliation: Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, United States.
authors.forename: Ari
authors.initials: A
authors.lastname: Romano-Verthelyi
authors.affiliation: Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Sand
authors.affiliation: Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, United States; Research and Development Service, Department of Veterans Affairs, VA Maryland Health Care System, Baltimore, MD, United States. Electronic address: ltonelli@psych.umaryland.edu.
authors.forename: Leonardo H
authors.initials: LH
authors.lastname: Tonelli
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D004644:Emotions / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D055809:Illness Behavior / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013550:Swimming / Q000523:psychology; D013997:Time Factors
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C499308:Rag2 protein, mouse; D003345:Corticosterone
keywords: Corticosterone; Cytokines; Forced swim test; Microglia; Open field test; T cells