Social Isolation-Induced Aggression Potentiates Anxiety and Depressive-Like Behavior in Male Mice Subjected to Unpredictable Chronic Mild Stress

Abstract

BackgroundAccumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that social isolation in male mice results in aggressive behavior. However, it is not known how social isolation-induced aggression affects anxiety and depressive-like behavior in isolated male mice subjected to unpredictable chronic mild stress (CMS), an animal model of depression.Methodology/Principal FindingsC57/B6 male mice were divided into 3 groups; non-stressed controls, in Group I; isolated mice subjected to the CMS protocol in Group II and aggression by physical contact in socially isolated mice subjected to the CMS protocol in Group III. In the sucrose intake test, ingestion of a 1% sucrose solution by mice in Groups II and III was significantly lower than in Group I. Furthermore, intake of this solution in Group III mice was significantly lower than in Group II mice. In the open field test, mice in Group III, showed reduced locomotor activity and reduced entry and retention time in the central zone, compared to Groups I and II mice. Moreover, the distances moved in 1 hour by Group III mice did not differ between night and morning. In the light/black box test, Groups II and III animals spent significantly less time in the light box compared to Group I animals. In the tail suspension test (TST) and forced swimming test (FST), the immobility times of Group II and Group III mice were significantly longer than in Group I mice. In addition, immobility times in the FST were significantly longer in Group III than in Group II mice.Conclusions/SignificanceThese findings show that social isolation-induced aggression could potentiate anxiety and depressive -like behaviors in isolated male mice subjected to CMS.

Behavioral and molecular alterations in mice resulting from chronic treatment with dexamethasone: Relevance to depression

“…Second, because mice were housed five per cage, maintaining animals in separate cages may have caused social isolation stress. Matsumoto et al (2005) showed that isolation stress induces aggression in mice, and Ma et al (2011) reported that this type of gained aggression potentiates depressive-like behavior and anxiety. Increased anxiety might have caused the reduction of the intake of saccharin.…”

The adaptive and maladaptive continuum of stress responses – a hippocampal perspective

“…Multiple animal models of chronic stress, including social defeat (Rygula et al, 2005), restraint stress (Strekalova et al, 2004;Wood et al, 2008) and CUS (Kompagne et al, 2008;Bessa et al, 2009), exhibit behavioral endophenotypes of major depression including behavioral despair, anhedonia and social avoidance ( Figure 1D). Further, animals subjected to social isolation or CUS also exhibit enhanced anxiety (Koike et al, 2009;Ma et al, 2011) (Figure 1D), and potentiated fear and startle behavior (McGuire et al, 2010). While exposure to a variety of chronic or acute severe stressors evokes depressive and anxiogenic behavioral phenotypes, it is important to note that the nature and intensity of behavioral effects are dependent on both the specific stressor paradigm (Table 1), and the genetic background and epigenetic landscape of the animal (Chaudhury et al, 2014;O'Leary et al, 2014).…”

“…Acute restraint or tail shock stress enhances hippocampal CA1 neuron spinogenesis in males ) ( Figure 2B). While it is unclear if acute stress-mediated spinogenesis exerts an adaptive Watanabe et al, 1992;Luine et al, 1994;Magarinos et al, 1997;Pavlides et al, 2002;Strekalova et al, 2004;Pawlak et al, 2005;Atif et al, 2008;Wood et al, 2008;Veena et al, 2009;Christian et al, 2011;Liu et al, 2012;Hillerer et al, 2013 CUS ( -Behrens et al, 1994;Sousa et al, 2000;Lee et al, 2006;Holderbach et al, 2007;Kompagne et al, 2008;Bessa et al, 2009;de Vasconcellos-Bittencourt et al, 2011;Gong et al, 2011;Ma et al, 2011 Social stressors (social defeat, severe fatal social stressor) Decreased dendritic complexity, decreased CA3 neuron dendritic length. Depl...…”

Effects of amycenone on serum levels of tumor necrosis factor-α, interleukin-10, and depression-like behavior in mice after lipopolysaccharide administration

“…After over all test, mice were replaced in to their home cages and returned to breeding room. The FST and TST in mice are the most widely used behavioral assays for detecting potential antidepressant-like activity (Cryan and Holmes, 2005;Ma et al, 2011Ma et al, , 2013Ma et al, , 2014Zhang et al, 2015).…”