Effects of co-administration of fluoxetine and risperidone on properties of peritoneal and pleural macrophages in rats subjected to the forced swimming test

Background: Literature data show that administration of atypical antipsychotic drug, risperidone (RIS), enhances antidepressive action of fluoxetine (FLU). As antidepressive treatments also regulate immune functions, we examined whether combined administration of FLU and RIS to rats subsequently subjected to a forced swimming test (FST) modifies parameters of macrophage activity that are directly related to their immunomodulatory functions, i.e., arginase (ARG) activity and nitric oxide (NO) synthesis. Methods: Antidepressive action of the drugs was assessed with FST. Peritoneal and pleural cells were eluted and selected parameters of immunoreactivity were assessed colorimetrically. Results: We found that the concomitant administration of FLU (10 mg/kg) and RIS (0.1 mg/kg) produced antidepressive-like effects in the FST, whereas the drugs were ineffective if administered separately. Stress related to the FST affected immune cell redistribution and changed some of the metabolic and immunomodulatory properties of macrophages. FLU administered to rats at a suboptimal dose for antidepressive action potently influenced macrophage immunomodulatory properties and redirected their activity toward anti-inflammatory M2 functional phenotype, as manifested by changes in the ARG/NO ratio. These effects resulted from a direct cellular influence of the drug, as well as its action via neuroendocrine pathways, as evidenced in peritoneal and pleural cells. Addition of RIS did not augment immunomodulatory action of FLU, though the combination showed antidepressant-like activity in the FST. Conclusions: Our results suggest that when the drugs were administered together, FLU was potent enough to redirect macrophages toward M2 activity. It is also postulated that drug-induced changes in the immune system are not so closely related to antidepressant-like effects or might be secondary to those produced in the neuroendocrine system.