Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior

Maïté Moreau, Caroline André, Jason C. O’Connor, Sara A. Dumich, Jeffrey A. Woods, Keith W. Kelley, Robert Dantzer, Jacques Lestage, Nathalie Castanon
Brain, Behavior, and Immunity. 2008-10-01; 22(7): 1087-1095
DOI: 10.1016/j.bbi.2008.04.001

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1. Brain Behav Immun. 2008 Oct;22(7):1087-1095. doi: 10.1016/j.bbi.2008.04.001. Epub
2008 May 13.

Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of
sickness behavior followed by chronic depressive-like behavior.

Moreau M(1), André C(1), O’Connor JC(2), Dumich SA(3), Woods JA(3), Kelley KW(4),
Dantzer R(4), Lestage J(1), Castanon N(5).

Author information:
(1)INRA, UMR 1286 PsyNuGen, Bâtiment UFR Pharmacie – 2° Tranche – 2° Etage, Case
courrier 34, Université Victor Ségalen Bordeaux 2, 146 rue Léo Saignat, CNRS, UMR
5226, IFR8, F-33076 Bordeaux, France.
(2)Integrative Immunology and Behavior Program, Department of Animal Sciences,
College of Agricultural, Environmental and Consumer Sciences, College of
Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
(3)Department of Kinesiology, College of Applied Health Studies, College of
Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
(4)Integrative Immunology and Behavior Program, Department of Animal Sciences,
College of Agricultural, Environmental and Consumer Sciences, College of
Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA;
Department of Pathology, College of Medicine, University of Illinois at
Urbana-Champaign, Urbana, IL 61801, USA.
(5)INRA, UMR 1286 PsyNuGen, Bâtiment UFR Pharmacie – 2° Tranche – 2° Etage, Case
courrier 34, Université Victor Ségalen Bordeaux 2, 146 rue Léo Saignat, CNRS, UMR
5226, IFR8, F-33076 Bordeaux, France. Electronic address:
.

Although cytokine-induced sickness behavior is now well-established, the
mechanisms by which chronic inflammation and depression are linked still remain
elusive. Therefore this study aimed to develop a suitable model to identify the
neurobiological basis of depressive-like behavior induced by chronic
inflammation, independently of sickness behavior. We chose to measure the
behavioral consequences of chronic inoculation of mice with Bacillus
Calmette-Guerin (BCG), which has been shown to chronically activate both lung and
brain indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme that
mediates the occurrence of depressive-like behavior following acute innate immune
system activation. BCG inoculation induced an acute episode of sickness
(approximately 5 days) that was followed by development of delayed
depressive-like behaviors lasting over several weeks. Transient body weight loss,
reduction of motor activity and the febrile response to BCG were dissociated
temporarily from a sustained increase in the duration of immobility in both
forced swim and tail suspension tests, reduced voluntary wheel running and
decreased preference for sucrose (a test of anhedonia). Moreover, we show that a
distinct pattern of cytokine production and IDO activation parallels the
transition from sickness to depression. Protracted depressive-like behavior, but
not sickness behavior, was associated with sustained increase in plasma
interferon-gamma and TNF-alpha concentrations and peripheral IDO activation.
Together, these promising new data establish BCG inoculation of mice as a
reliable rodent model of chronic inflammation-induced depressive-like behaviors
that recapitulate many clinical observations and provide important clues about
the neurobiological basis through which cytokines may have an impact on affective
behaviors.

DOI: 10.1016/j.bbi.2008.04.001
PMCID: PMC2908297
PMID: 18479887 [Indexed for MEDLINE]

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