Exacerbated glucocorticoids and cytokines action are essential factor in the pathogenesis of depression, and the effects of antidepressant drugs on these parameters are poorly recognized.We investigated the effect of antidepressant drugs on the HPA axis activity in prenatally stressed S-D rats and on cell-mediated immunity in Wistar rats and C57BL/6 mice subjected to chronic mild stress (CMS) model of depression. The activity of HPA axis was estimated by measuring the level of glucocorticoid receptors (GR) and activity of some kinases which are known to infl uence GR action. Adult rats subjected to prenatal stress displayed prolonged immobility in the Porsolt test and in open-fi eld test, elevated corticosterone level, increased GR level in the hippocampus but not in frontal cortex. They also showed decreased FKBP51 in the frontal cortex, but not in hippocampus, decreased the active, phosphorylated form of the JNK1 and 2 kinase in the hippocampus and the active form of p38-MAPK in the frontal cortex. Chronic imipramine, fl uoxetine, mirtazapine or tianeptine administration normalized most of these parameters. In CMS model of depression anti-anhedonic effect of imipramine was accompanied by decreased proliferative activity of splenocytes and their ability to produce pro-infl ammatory cytokines in rats. In desipramine treated mice subjected to CMS increased ability of T cells to produce negative immunoregulator IL-10 and decreased the cytotoxic activity of NK cells were observed.
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