Social status in mice: behavioral, endocrine and immune changes are context dependent Alessandro Bartolomucci a,b, *, Paola Palanza a , Leda Gaspani c , Elena Limiroli c , Alberto E. Panerai c , Graziano Ceresini d , Marco D. Poli b , Stefano Parmigiani a a Dipartimento di Biologia Evolutiva e Funzionale, Universita Á di Parma, Parco Area delle Scienze 11A, 43100 Parma, Italy b Istituto di Psicologia, Universita Á di Milano, Via T. Pini 1, 20134 Milan, Italy c Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica, Universita Á di Milano, Via Vanvitelli 32, 20129 Milan, Italy d Dipartimento di Medicina Interna e Scienze Biomediche, Universita Á di Parma, Via Gramsci 14, 43100 Parma, Italy Received 9 October 2000; accepted 8 February 2001 Abstract The aim of the present study was to investigate the effect of social status on the endocrine, immune and behavior response of male mice. We found that in mice reared in a group of siblings since weaning, no difference exists between dominants and subordinates in basal corticosterone level, in behavior in the open-field test OFT) and in a series of immune parameters. These results suggest that living with siblings is not a stressful condition for either dominant or subordinate mice. Therefore, group-housed siblings can be regarded as a valid control group in social stress studies. When mice were subjected to chronic psychosocial stress for 21 days, four types of social outcome occurred: residents becoming dominants, intruders becoming subordinates, residents becoming subordinates and intruders becoming dominants. Interestingly, the behavioral profile in the OFT revealed a status-dependent effect, with resident dominants RD) and intruder dominants InD) showing the highest locomotor and exploratory activity, whereas the corticosterone level was higher than control for all four categories. In addition, a context-dependent effect emerged at the immune level: resident subordinates RS) had a reduced splenocyte proliferation and IL-4 and IL-10 production. Mice in all the other three social ranks showed no immune alterations. Therefore, the loss of an individual's social rank position seems a promising field of study to investigate the psychological impact of stressful events. D 2001 Elsevier Science Inc. All rights reserved. Keywords: House mouse; Social status; Psychosocial stress; Group housing; Control group; Open field; Corticosterone; Splenocyte proliferation; IL-4; IL-10; IL-2; IFN-g; b-Endorphin 1. Introduction Interest in the impact of stress on social animals have led to the development of several social stress models that may be relevant to human stress-related disease [1,2] see also Fuchs et al., this issue). From the Resident/Intruder Test [3] to the Visible Burrow System [4], the Chronic Psychosocial Stress [5] and the Sensory Contact Model [6], the main focus has been on the effect of the fight- induced subordination see Ref.[1] for review). As a result, the concept of subordination stress [7,8] has become widely popular and the most studied model in examining the effects of social threat. Subordination, however, cannot be regarded as a unique concept. For example, rats showing submissive and subdominant be- havioral patterns [9] show different, and sometimes oppo- site, neuroendocrine and immune alterations [10,11]. In addition, dominants, or winners of aggressive interactions, can show signs of behavioral and physiological stress- induced alterations [4,12]. Finally, quantitative and qual- itative differences in social threat exist depending on the type of opponent and on the intensity of the aggressive act [13,14]. The complex picture emerging so far claims for an in-depth analysis of the social contexts and the individual factors responsible for the development of stress-related alterations. Koolhaas et al. [9] revealed that different stress responses and risks in developing pathol- 0031-9384/01/$ ± see front matter D 2001 Elsevier Science Inc. All rights reserved. PII:S0031-938401)00453-X * Corresponding author. Dipartimento di Biologia Evolutiva e Funzionale, Universita Á di Parma, Parco Area delle Scienze 11A, 43100 Parma, Italy. Tel.: +39-0521-905-629; fax: +39-0521-905-657. E-mail address: bartolomucci@biol.unipr.it A. Bartolomucci). Physiology & Behavior 73 2001) 401±410