Feeding, exploratory, anxiety- and depression-related behaviors are not altered in interleukin-6-deficient male mice

Abstract

Interleukin-6 (IL-6) has been implicated in behavioral responses associated with inflammation, sickness behavior and various nervous system disorders. We studied a range of different behaviors in IL-6-knockout (IL-6ko) and wild-type (WT) male mice. No significant differences were observed in ambulatory, exploratory, and stereotypic activities in home or novel cages, in an open field (OF), in the multicompartment chamber (MCC), or in the elevated plus-maze (EPM). IL-6ko mice shed fewer fecal boli than WT mice in the OF, in novel cages and in the MCC although this effect was not statistically significant in the OF. In novel cages, intraperitoneal (i.p.) injection of IL-6 (1 μg) depressed ambulatory activity slightly more in IL-6ko than in WT mice. Restraint and interleukin-1β (IL-1β, 100 ng i.p.) decreased exploration of mice in the MCC and EPM, but there was no indication of altered sensitivity in IL-6ko mice. No significant differences were detected in the tail suspension and the Porsolt forced swim tests. IL-1β and lipopolysaccharide (LPS 1 μg i.p.) injection depressed sweetened milk and solid food intake similarly in IL-6ko and WT mice, but IL-6 had no effect, suggesting that IL-6 is not involved in these effects of IL-1 or LPS. However, IL-1β and LPS depressed body weight more in WT than in IL-6ko mice. Plasma corticosterone and basal concentrations of catecholamines, indoleamines and their metabolites in several brain regions were similar. The responses in these measures to IL-1β and LPS were also similar, except that there were no significant changes in tryptophan and serotonin metabolism in IL-6ko mice. This may reflect a role for IL-6 in the tryptophan and serotonin responses to IL-1 and LPS. It is concluded that the lack of IL-6 is not associated with substantial alterations in several different mouse behaviors, and in the responses to restraint, IL-1β, IL-6 and LPS.

Astrocytic IL-6 mediates locomotor activity, exploration, anxiety, learning and social behavior

“…An inverse correlation between anxiety and depression had already been suggested for rats with low anxiety (Prasad et al, 1997). On the contrary, no significant differences between genotypes were observed in young mice, which in fact is also consistent with a previous study with young total IL-6 KO mice at 6 weeks of age (Swiergiel and Dunn, 2006). Altogether, those results suggest that age is a crucial factor in mediating IL-6 role in depression-like behaviors.…”

“…Another group confirmed the decrease in rearings and the increase in anxiety using the same IL-6 KO mice, but these authors found opposite results regarding locomotion (Butterweck et al, 2003). Other authors observed altered exploration and anxiety levels of IL-6 KO mice depending on the specific settings (Baier et al, 2009;Butterweck et al, 2003), or genetic background (Swiergiel and Dunn, 2006).…”

Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice

“…However, the fact that cytokine-induced increased serotonin turnover is dependent on diffuse microglial activation does not favor such a possibility, since there is usually no difference in turnover rates between different brain areas following immune stimulation. 46 The lack of an effect on serotonin turnover does not preclude the possibility of more subtle cytokineinduced alterations in serotoninergic neurotransmission, as might be caused by increases in serotonin transporter expression 47 or modulation of specific serotonin receptor subtype 47 or sensitivity. Studies designed to specifically examine the effects of LPS and IDO activation on the temporal and spatial patterns of 5-HT-related processes in discrete brain regions still need to be carried out before being able to dismiss a possible serotoninergic component in the pathophysiology of LPS-induced depressive-like behavior.…”

Central blockade of melanocortin receptors attenuates the metabolic and locomotor responses to peripheral interleukin-1β administration

“…This manuscript describes the simultaneous measurement of numerous metabolic responses to evaluate both energy intake and energy expenditure (food and water intake, locomotor activity, oxygen consumption and respiratory exchange ratio (RER)). Further, we have chosen to examine single cytokine administration (IL-1β and TNF-α, as IL-6 may be less important in mediating immune-associated metabolic changes (Swiergiel and Dunn, 2006), in an effort to determine which metabolic parameters are affected by each cytokine.…”