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Physiol Behav. 2006 Jun 15;88(1-2):108-15. Epub 2006 May 2.

Variations in behavior, innate immunity and host resistance to B16F10 melanoma growth in mice that present social stable hierarchical ranks.

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  • 1Applied Pharmacology and Toxicology Laboratory, Department of Pathology, School of Veterinary Medicine, University of São Paulo, SP, Brazil.


The present study analyzed the effect of social stable hierarchical dominance/submissive relationships in C57BL/6 mice on behavior, innate immunity, serum corticosterone levels and host resistance to B16F10 melanoma growth. Adult mice (90 days old) kept in pairs since weaning, were analyzed for dominant/submissive ranking in three consecutive days according to the presence or absence of fighting and/or anticipatory submissive responses. Only the pairs of mice where dominant/submissive relationships were clearly stated were employed. Results showed that submissive mice presented in relation to dominants: (1) decreased time spent in the central open-field area; (2) decreased number of entries into the open arms and decreased time spent in the exploration of the open arms of the plus maze; (3) increased time spent in exploration of the plus-maze closed arms; (4) decreased number of entries and in the time spent in the exploration of the third part of the plus-maze open arms; (5) increased number of B16F10 metastasis in the lungs; (6) decreased NK cell cytotoxicity measured in vitro in the peripheral blood and spleen; (7) decreased basal but not in S. aureus induced oxidative burst in both neutrophils and monocytes and (8) similar basal serum levels of corticosterone. The present behavioral findings show that submissive mice, within a stable social hierarchy, present anxiety like-responses a fact that would make than more prone to stressful stimuli. This condition would be responsible for the decreases presently observed on basal neutrophil oxidative burst, NK cell activity and resistance to B16F10 tumor growth. Together the obtained data show that mice that present stable hierarchical relationships display neuro-immune alterations comparable to those reported in mice under a situation of chronic social stress.

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