Abstract
Negative social experiences during adolescence increase the risk of psychiatric disorders in adulthood. Using “resident-intruder” stress, the present study aimed to investigate the effects of adolescent social defeat on emotional and cognitive symptoms associated with psychiatric disorders during adulthood and the effects of the developmental stage and social condition on this process. In Experiment 1, animals were exposed to social defeat or manipulation for 10 days during early adolescence (EA, postnatal days [PND] 28–37), late adolescence (LA, PND 38–47), and adulthood (ADULT, PND 70–79) and then singly housed until the behavioral tests. Behaviors, including social avoidance of the defeat context and cortically mediated cognitive flexibility in an attentional set-shifting task (AST), were assessed during the week following stress or after 6 weeks during adulthood. We determined that social defeat induced significant and continuous social avoidance across age groups at both time points. The mice that experienced social defeat during adulthood exhibited short-term impairments in reversal learning (RL) on the AST that dissipated after 6 weeks. In contrast, social defeat during EA but not LA induced a delayed deficit in extra-dimensional set-shifting (EDS) in adulthood but not during adolescence. In Experiment 2, we further examined the effects of social condition (isolation or social housing after stress) on the alterations induced by social defeat during EA in adult mice. The adult mice that had experienced stress during EA exhibited social avoidance similar to the avoidance identified in Experiment 1 regardless of the isolation or social housing after the stress. However, social housing after the stress ameliorated the cognitive flexibility deficits induced by early adolescent social defeat in the adult mice, and the social condition had no effect on cognitive function. These findings suggest that the effects of social defeat on emotion and cognitive function are differentially affected by the developmental stage and social condition. EA may comprise a particularly sensitive developmental period in which social defeat may produce a delayed impairment in cognitive flexibility during adulthood, and the social condition following stress appears to play an important intermediary role in the development of these cognitive deficits.
Highlights
In humans, bullying and subordination are prevalent stressors throughout life and are strongly related to the onset of psychiatric disorders (Brown and Prudo, 1981; Taylor et al, 2011)
We demonstrated that social defeat for 10 days (PND 70–79) induces deficits in reversal learning (RL) in the attentional set-shifting task (AST) in adult mice tested during the following week after the stress
Considering the specific effect of the orbitofrontal cortex (OFC) on RL, the results further suggested that the medial prefrontal cortex (mPFC) may comprise an area more sensitive to early adolescent stress compared with the OFC
Summary
In humans, bullying and subordination are prevalent stressors throughout life and are strongly related to the onset of psychiatric disorders (Brown and Prudo, 1981; Taylor et al, 2011). These disorders are clinically heterogeneous with distinct symptoms that reflect emotional and cognitive dysfunctions. Numerous studies have demonstrated that repeated exposure to social defeat elicits a set of depressive and anxious behaviors in adult rodents, including anhedonia, anxiety in the elevated plus maze and open field, and social avoidance (Buwalda et al, 2005; Venzala et al, 2012). The behavioral alterations induced by adult social defeat are not lasting and are reversible following a period of recovery (fear memories of the defeat context may last longer; Buwalda et al, 2005; Venzala et al, 2012; Snyder et al, 2015)
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