Behavioral and immunological effects of substance P in female and male mice

This study investigated whether the central injection of substance P (SP) promotes differential behavioral [elevated plus-maze (EPM), open-field and hole-board tests] or immunological effects [peripheral blood lymphocyte subsets and nitric oxide (NO) produced by macrophages] in male and female mice. The percentage of time spent on open arms was significantly reduced by SP treatment in female (87%) and male mice (68%). A similar effect was observed in the percentage of entries into open arms (55% and 30%, respectively), as well as in the head-dipping parameter (63% and 27%, respectively), suggesting that SP promoted an anxiogenic-like profile in both sexes, which are detectable only in the plus-maze test. Female mice showed a significant decrease (20%) in the absolute number of lymphocytes and leukocytes comparing with control group and male SP-treated animals (4% of reduction), although only SP-treated males presented an increase (100%) in NO production by macrophages. Thus, our data showed no apparent statistical difference on the anxiogenic-like profile of action induced by SP between female and male mice; notwithstanding, SP, depending on the immune parameter evaluated, differentially influenced both sexes. The implications of these findings, as well as the putative participation of proinflammatory cytokines in this phenomenon, are discussed. (C) 2004 Elsevier Inc. All rights reserved.