Dominance relationships in Syrian hamsters modulate neuroendocrine and behavioral responses to social stress

Abstract

Stress is a well-known risk factor for psychopathology and rodent models of social defeat have strong face, etiological, construct and predictive validity for these conditions. Syrian hamsters are highly aggressive and territorial, but after an acute social defeat experience they become submissive and no longer defend their home territory, even from a smaller, non-aggressive intruder. This defeat-induced change in social behavior is called conditioned defeat (CD). We have shown that dominant hamsters show increased neural activity in the ventromedial prefrontal cortex (vmPFC) following social defeat stress and exhibit a reduced CD response at social interaction testing compared to subordinates. Although the vmPFC can inhibit the neuroendocrine stress response, it is unknown whether dominants and subordinates differ in stress-induced activity of the extended hypothalamic-pituitary-adrenal (HPA) axis. Here, we show that, following acute social defeat, dominants exhibit decreased submissive and defensive behavior compared to subordinates but do not differ from subordinates or social status controls (SSCs) in defeat-induced cortisol concentrations. Furthermore, both dominants and SSCs show greater corticotropin-releasing hormone (CRH) mRNA expression in the basolateral/central amygdala compared to subordinates, while there was no effect of social status on CRH mRNA expression in the paraventricular nucleus of the hypothalamus or bed nucleus of the stria terminalis. Overall, status-dependent differences in the CD response do not appear linked to changes in stress-induced cortisol concentrations or CRH gene expression, which is consistent with the view that stress resilience is not a lack of a physiological stress response but the addition of stress coping mechanisms. Lay summary Dominant hamsters show resistance to the behavioral effects of acute social defeat compared to subordinates, but it is unclear whether social status modulates the neuroendocrine stress response in Syrian hamsters. This study indicates that dominant social status does not alter stress-induced activity of the extended hypothalamic-pituitary-adrenal (HPA) axis, which suggests that the ability of dominants to cope with social defeat stress is not associated with changes in their neuroendocrine stress response.

Dominance status alters restraint-induced neural activity in brain regions controlling stress vulnerability

“…We found no effect of social status on restraint-induced c-Fos expression in the PVN, which is similar to our previous findings using social defeat stress [24]. Likewise, we recently found that dominant and subordinate hamsters do not significantly differ in plasma cortisol concentrations immediately or 60 min following social defeat stress [38]. Furthermore, pharmacological blockade of glucocorticoid synthesis during social defeat stress does not alter the acquisition of the conditioned defeat response in hamsters [39].…”

Activity of a vmPFC-DRN Pathway Corresponds With Resistance to Acute Social Defeat Stress

“…In another animal model, optogenetic stimulation of the vmPFC-DRN circuit during an acute forced swim stressor promotes proactive behavioral responses (Warden et al, 2012), which have been argued to index stress resilience (e.g., Wood et al, 2010). In our laboratory, we have shown that male Syrian hamsters who maintain social dominance for 2 weeks exhibit fewer negative behavioral (Morrison et al, 2014), neuroendocrine (Dulka et al, 2018b), and neurochemical (Dulka et al, 2017) consequences of social defeat stress compared to subordinates or controls. Importantly, such status-dependent changes in behavior require recruitment of vmPFC neurons (Morrison et al, 2013) and correspond with reduced activity of the DRN during social and non-social acute stress (Cooper et al, 2017).…”

“…Behaviorally, resisting defeat coincides with decreased immobility in a forced swim test (Veenema et al, 2005;Wood et al, 2010), increased active avoidance in a shuttle box (Benus et al, 1989), active shock probe burial (Koolhaas et al, 2010), and reduced conditioned fear of the defeat context (Walker et al, 2008). Similarly, counterattacking aggressors during social defeat stress is associated with a reduced conditioned defeat response, marked by avoidance of and submission to a non-threatening social stimulus (Morrison et al, 2014;Dulka et al, 2018b).…”

Anxiolytic effect of minocycline in posttraumatic stress disorder model of Syrian hamsters

“…We used Syrian hamsters as they are inherently territorial and solitary in nature [ 20 ]. Second, on confrontation of smaller and larger hamsters in latter's cage, the larger hamster rarely physically injures the smaller hamster and both the hamsters exhibit characteristic ritualistic agnostic behavior (dominance and submission) [ Table 2 ].…”