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The content of pro- and anti-inflammatory cytokines in the hypothalamus, hippocampus, and blood serum of C57Bl/6J mice with depressive-like behavior induced by 20-day social stress was analyzed in 4 h after immune stimulation with LPS (250 μg/kg). These animals are characterized by a tendency to an increase in the blood content of IL-6 and a decrease in the level of IL-10. Changes in cytokine content in the brain of mice with depressive-like state developed under these conditions were observed only in the hippocampus: the levels of IL-1β, IL-6, TNFα, and IL-10 increased and the content of IFNγ decreased in comparison the corresponding parameters in the controls (not exposed to social stress) and aggressive animals. No changes in the levels of IL-2, IL-4, and IL-17 were revealed in the hypothalamus and hippocampus.

We studied the influence of depression-like behavior developed in C57BL/6J mice under conditions of social stress of different duration on cytokine production by splenic cells. Imbalance of the pro- and anti-inflammatory cytokines was detected at the early stage of depression-like behavior (10-day experience of defeats): increased production of proinflammatory IL-2 and IL-6 cytokines along with a decrease in anti-inflammatory IL-10 level; the levels of IL-1β, TNFα, IFNγ, and IL-4 remained unaffected. At later terms (20 days of confrontations), we revealed more pronounced changes in spontaneous production of proinflammatory cytokines that were not detected after shorter social stress. These findings suggest that cytokine profile depends on duration of social stress. Possible mechanisms of cytokine production during formation of depression-like state are discussed.

We studied activity of lysosomal cysteine proteases, cathepsins B and L, in brain structures (frontal cortex, caudate nucleus, hippocampus, and hypothalamus) of C57Bl/6J mice with aggressive and depressive-like behavior formed under conditions of chronic social stress (repeated experience of victories and defeats within 20 days). Mice with depressive-like behavior showed increased activity of cathepsin В in the hypothalamus and nucleus caudatus and increased activity of cathepsin L in the hippocampus compared to control animals not subjected to agonistic confrontations. In mice with aggressive behavior, protease activity in the studied brain structures was not changed. In 4 h after immune system activation with LPS (250 μg/kg), cathepsin L activity in the hippocampus of control mice increased in comparison with mice receiving saline. In contrast to control animals, LPS caused a decrease in activity of the enzyme in the caudate nucleus and frontal cortex of aggressive mice and in the hippocampus of mice with depressive-like behavior.

The effect of chronic treatment with antidepressant drugs fluoxetine (20 mg/kg) and imipramine (25 mg/kg) on the number of antibody-producing cells and the main T cell subpopulations in ASC mice characterized by genetic predisposition to depression-like states was studied at the peak of the SE-induced immune response (5×10(8)). Fluoxetine produced an immunostimulatory effect manifested in an increase in the relative and absolute number of IgM antibody-producing cells in the spleen and index of immunoreactivity (CD4/CD8). Administration of fl uoxetine to parental mouse strains without depression (CBA and AKR) had no effect (CBA) or reduced the immune response. The CD4/CD8 ratio did not increase under these conditions. Imipramine was ineffective in the correction of immune reactions in a depression-like state.