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.

Involvement of tachykinin NK1 receptor in the behavioral and immunological responses to swimming stress in mice.

This study investigated the influence of a selective tachykinin NK(1) receptor antagonist FK888 on the performance of mice in the elevated plus-maze test and on peripheral blood count after central treatment with substance P (SP) compared to animals submitted to a swim stress session. Percentage of time spent on open arms was significantly reduced by SP treatment as well as the percentage of entries into open arms and the number of head-dipping, indicating an anxiogenic-like profile of action to SP, as previously described. Nevertheless, SP did not affect the peripheral blood counting. The swim stress also promoted a marked reduction in the exploration of the open arms of the plus-maze as well as in the number of leukocytes, most notably lymphocytes. FK888 alone showed the reverse effect, i.e. an anxiolytic-like profile, increasing the frequency of entries and the time spent in the open arms, but did not affect the blood parameters used as an index of the immune system activity. Nevertheless, FK888 (100 pmol) inhibited the anxiogenic-like profile of SP and swimming stress and also prevented the effect promoted by the swimming stress on the immunological parameters, i.e., the reduction in the number of peripheral leukocytes. These findings are discussed in terms of the interaction between the CNS and the immune system and the involvement of the tachykininergic system.