Repeated social defeat causes increased anxiety-like behavior and alters splenocyte function in C57BL/6 and CD-1 mice

Abstract

The experimental model, social disruption (SDR), is a model of social stress in which mice are repeatedly attacked and defeated in their home cage by an aggressive conspecific. In terms of the impact of this stressor on the immune response, SDR has been reported to cause hyperinflammation and glucocorticoid insensitivity. To this point however, the behavioral consequences of SDR have not been thoroughly characterized. Because social defeat has been reported to cause anxiety-and depressive-like behaviors, the current study was designed to assess whether SDR also causes anxietyand depressive-like behaviors. Using the light/dark preference test and the open field test as tools to measure behaviors characteristic of anxiety, the data showed that C57BL/6 and CD-1 male mice subjected to SDR displayed increased anxiety-like behavior. The increase in anxiety-like behaviors persisted for at least one week after the cessation of the stressor. In contrast, depressive-like behaviors were not elicited by SDR as assessed by the forced swim test or the tail suspension test. These data indicate that social disruption stress causes an increase in anxiety-like behaviors, but not depressivelike behaviors.

Subordinate social status modulates the vulnerability to the immunological effects of social stress

“…The splenic response to SDR varied significantly between individuals undergoing defeat in similar conditions (Avitsur et al, , 2003bBailey et al, 2004, Kinsey et al, 2007. Following SDR, some of the mice exhibited significant changes in splenocytes phenotype and function, while their cage mates were hardly affected .…”

Psychological stress and cancer

“…The data identified infiltrating macrophage as a key intermediate in stress-induced tumor cell metastasis, demonstrating the important relationship between behavioral stress, immune system, and disease outcomes. Moreover, although the effect of psychosocial stress on cancer is largely unexplored, social disruption (SDR) stress animal model has been effective in predicting its impact on disease and behavior, including the response to influenza viral infection (Mays et al 2010(Mays et al , 2012Powell et al 2011) and pronounced anxiety-like behavior in mice exposed to SDR (Curry et al 2010;Engler et al 2005;Wohleb et al 2011;Kinsey et al 2007;Avitsur et al 2002). Stress itself could induce significant lung inflammation in mice experiencing SDR (Curry et al 2010).…”

“…In vivo mouse models of stress have made a significant progress in determining the mechanisms of stress-induced alterations in inflammatory immune responses; a social disruption (SDR) stress mouse model of repeated social defeat has linked stress to triggering the generation, egress, and trafficking of immature, inflammatory myeloid-derived cells that are glucocorticoid (GC) insensitive (Curry et al 2010;Engler et al 2004aEngler et al , 2005 and produce high levels of IL-6 and other inflammatory cytokines and chemokines (Powell et al 2009;Stark et al 2002;Wohleb et al 2011). These stress-induced changes in the sympathetic nervous system (SNS) led to significant immune and prolonged anxiety-like behavior changes (Wohleb et al 2011;Bailey et al 2007, 2009a, 2009b, Dong-Newsom et al 2010Kinsey et al 2007;Mays et al 2010Mays et al , 2012Powell et al 2011), and could be reversed by the blockade of sympathetic signaling prior to stressor exposure (Wohleb et al 2011). Studies involving both animals and humans suggest that natural killer (NK) cells are particularly important in the elimination of metastatic tumor cells (Whiteside and Herberman 1989;Page et al 1994).…”

Individual contribution of metabotropic glutamate receptor (mGlu) 2 and 3 to c-Fos expression pattern evoked by mGlu2/3 antagonism

“…A possible explanation for these discrepancies may be the different genetic background of the mice used in the two studies: Linden used the CD1 mouse strain, whereas for our study, we used mice backcrossed into the C57Bl/6 background. These two mouse strains show important behavioral differences in stress-and anxiety-related tests, such as predator-induced freezing and risk assessment and exploration in the light dark box (e.g., Yang et al 2004;Kinsey et al 2007), which may produce also differential neuronal activation upon exposure to stress and/or drugs. Indeed, a recent experiment carried out in our lab showed strain-dependent differential neuronal activation in response to stress, e.g., by exposure to aversive stimuli (Hetzenauer and Singewald, unpublished).…”