Article The role of forced swim test on neutrophil leukocytosis observed during inflammation induced by LPS in rodents Sonia P. Altenburg a, *, Diana G. Ventura a , Vilma A. Da-Silva a , Luciana R. Malheiros a , Hugo C. Castro-Faria-Neto b , Patrı ´cia T. Bozza b , Nancy A. Teixeira c a Departamento de Fisiologia e Farmacologia, Instituto Biome ´dico, Universidade Federal Fluminense, Rua Ernani Melo 101, S. Domingos, 24210-130 Nitero ´i, RJ, Brazil b Departamento de Fisiologia e Farmacodina ˆmica, FIOCRUZ, Rio de Janeiro, Brazil c Departamento de Farmacologia, Faculdade de Cie ˆncias Me ´dicas, UNICAMP, Campinas, Brazil Abstract Adult male rats were administered intrapleural (ipl) or intraperitoneal (ip) injection of lipopolysaccharide (LPS), 24 h after being submitted to forced swim test (FST). Four hours after LPS challenge, an increase in pleural and peritoneal leukocyte and neutrophil counts in animals not exposed to FST was noted. FST induced a marked increase in pleural, but not in peritoneal, neutrophil leukocytosis. The results suggest that lowered mood may increase inflammatory response to LPS. D 2002 Elsevier Science Inc. All rights reserved. Keywords: Depression; Forced swim test; Inflammation; LPS; Neutrophils; Rodent 1. Introduction For the last two decades, a series of studies demonstrating that mood disorders may modify immune and inflammatory functions and affect susceptibility to physical illness have been produced (Khansari et al., 1990; Tecoma and Huey, 1985; Maes et al., 1992a,b). In general, results of these studies suggested that stress and depression might decrease the immune function and its responses. Believing this hypothesis, Steplewski and Vogel (1986) demonstrated a decrease in the total number of lymphocytes in rats exposed to a stressful condition. The same effect was observed in patients submitted to stressful situations (Connor and Leo- nard, 1998). Irwin et al. (1990) demonstrated that depression was associated to impaired immune function because the activity of natural killer (NK) cells of depressive patients was reduced. It has been currently reported that immunosuppres- sion explains the relationships between depression and susceptibility to physical illness. However, there are eviden- ces that depression may be associated with activation of the immune system and its responses (i.e. inflammation) (Maes et al., 1999). In this context, several studies that examined total and differential white blood cells counts showed an immune cell profile that was indicative of immune activa- tion. For instance, Irwin et al. (1990) and Kronfol and House (1989) noted marked leukocytosis that was accompanied by neutrophilia during depression in humans. Although the great number of evidence already suggests that human depression may result also in immune stimu- lation and increase in inflammatory responses, studies carried out under controlled experimental conditions are still lacking. Thus, in the present study, we used an experimental model of depression described by Porsolt et al. (1977), the forced swim test (FST), to evaluate leuko- cyte, mainly neutrophils, trafficking in the body using the models of pleurisy and peritonitis induced by local injection of lipopolysaccharide (LPS) in rats. 2. Methods 2.1. Animals Male Wistar rats (Laboratory of Behavioral and Devel- opmental Sciences Breeding Unit from Universidade Fed- 0278-5846/02/$ – see front matter D 2002 Elsevier Science Inc. All rights reserved. PII:S0278-5846(01)00335-9 Abbreviations: FST, forced swim test; CFST, complete FST; LPS, lipopolysaccharide; FSV, first swimming vehicle; NSV, nonswimming vehicle; FSL, first swimming LPS; NSL, nonswimming LPS; TNFa, tumor necrosis factor a; NK, natural killer; IL-1, interleukin-1 * Corresponding author. Fax: +55-21-6205266. E-mail address: mflsalt@vm.uff.br (S.P. Altenburg). Progress in Neuro-Psychopharmacology & Biological Psychiatry 26 (2002) 891 – 895