BRAIN, BEHAVIOR, AND IMMUNITY 11, 107–118 (1997) ARTICLE NO. BI970485 Differential Effects of Lipopolysaccharide on Pup Retrieving and Nest Building in Lactating Mice Arnaud Aubert, Glyn Goodall, Robert Dantzer, and Gilles Gheusi INRA-INSERM U394, Domaine de Carreire, Rue Camille Saint-Sae ¨ns, 33077 Bordeaux Cedex, France Behavioral symptoms of sickness that develop in response to lipopolysaccharide (LPS) and proinflammatory cytokines include depressed locomotion, anorexia, and reduced social activities. The way maternal behavior is affected in response to cytokines has, however, not yet been investigated. We checked that lactating mice are sensitive to LPS by showing that LPS- (400 mg/kg, ip) injected mice ate and drank less than saline-injected mothers and displayed a decreased rectal temperature. At an ambient temperature of 22°C, nest building was significantly decreased in LPS-treated mothers compared to saline-treated animals, whereas pup retrieving, while slower, was still present and globally as efficient as for saline-treated mice. In a second experiment, dams were either injected with physiological saline or LPS but were also exposed to a cold ambient temperature (6°C) or kept in standard external condition (22°C). LPS-treated mice exposed to cold expressed not only pup-retriev- ing but also nest-building activity. These differential results indicate that the behavioral expression of LPS-induced sickness depends on the priority of the behavior under consider- ation.  1997 Academic Press INTRODUCTION Animals infected with pathogen microorganisms show various behavioral symptoms of sickness, including lethargy, anorexia, adipsia, and reduced social interest (Plata- Salama `n, 1988; Kluger, 1991; Bluthe ´, Parnet, Dantzer, & Kelley, 1992). The same symptoms can be observed in response to lipopolysaccharide (LPS), the active frag- ment of endotoxin, or the recombinant proinflammatory cytokines this bacterial frag- ment induces (e.g., interleukin-1, interleukin-6, tumor necrosis factor) (Kent, Bluthe ´, Dantzer, Hardwick, Kelley, Rothwell, & Vannice, 1992). Hart (1988) has convincingly argued that the behavioral alterations that develop during infection are not simply a consequence of a reduced efficiency of bodily functions but that sickness behavior, to use the terminology he proposed, supports the metabolic and physiological changes that occur in the infected organism and increases their efficiency. This means that the reduced behavioral activities that are observed in sick individuals are not the result of weakness and physical debilitation which accompany sickness, but represent a set of coordinated responses in face of infection and inflammation. This view puts sickness behavior in the category of motivated behaviors (Dantzer & Satinoff, 1994). The study of the motivational aspects of sickness behavior has so far focused exclusively on self-directed behaviors, i.e., those behavioral changes which provide direct benefit to the sick individual. There has been no attempt to investigate the consequences of sickness on behaviors such as maternal behavior. For the purpose of this study, we selected two components of pup-caring behavior with different priorities for the survival of the litter: pup retrieving and nest building. Although these behavioral activities can be expressed by nonmaternal animals in contexts other than maternal care, the fact that they were elicited in lactating dams in a situation in which the litter 107 0889-1591/97 $25.00 Copyright  1997 by Academic Press All rights of reproduction in any form reserved.