title: Prolonged depression-like behavior caused by immune challenge: influence of mouse strain and social environment.
abstract: Immune challenge by bacterial lipopolysaccharide (LPS) causes short-term behavioral changes indicative of depression. The present study sought to explore whether LPS is able to induce long-term changes in depression-related behavior and whether such an effect depends on mouse strain and social context. LPS (0.83 mg/kg) or vehicle was administered intraperitoneally to female CD1 and C57BL/6 mice that were housed singly or in groups of 4. Depression-like behavior was assessed with the forced swim test (FST) 1 and 28 days post-treatment. Group-housed CD1 mice exhibited depression-like behavior 1 day post-LPS, an effect that leveled off during the subsequent 28 days, while the behavior of singly housed CD1 mice was little affected. In contrast, singly housed C57BL/6 mice responded to LPS with an increase in depression-like behavior that was maintained for 4 weeks post-treatment and confirmed by the sucrose preference test. Group-housed C57BL/6 mice likewise displayed an increased depression-like behavior 4 weeks post-treatment. The behavioral changes induced by LPS in C57BL/6 mice were associated with a particularly pronounced rise of interleukin-6 in blood plasma within 1 day post-treatment and with changes in the dynamics of the corticosterone response to the FST. The current data demonstrate that immune challenge with LPS is able to induce prolonged depression-like behavior, an effect that depends on genetic background (strain). The discovery of an experimental model of long-term depression-like behavior after acute immune challenge is of relevance to the analysis of the epigenetic and pathophysiologic mechanisms of immune system-related affective disorders.
authors.affiliation: Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
authors.forename: Evelin
authors.initials: E
authors.lastname: Painsipp
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Köfer
authors.forename: Frank
authors.initials: F
authors.lastname: Sinner
authors.forename: Peter
authors.initials: P
authors.lastname: Holzer
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects / Q000276:immunology; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D005518:Food Preferences / Q000187:drug effects; D006799:Housing, Animal; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D012931:Social Environment; D013045:Species Specificity; D013395:Sucrose; D013997:Time Factors
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D013395:Sucrose; D003345:Corticosterone