Cardiovascular outcomes related to social defeat stress: New insights from resilient and susceptible rats

Abstract

Stress exposure is an important risk factor for psychiatric and cardiovascular disorders. Two phenotypes related to coping with stress can be observed in rodents that experience chronic social defeat stress (SDS): susceptible, showing social avoidance and behavioral changes related to depression, and resilient, showing none of these alterations. Moreover, a strong correlation exists between depression and the development of or mortality due to cardiovascular diseases. Nevertheless, little is known about cardiovascular alterations related to SDS exposure in those phenotypes or their correlation with depressive-like behaviors. Using a chronic SDS protocol followed by the social interaction test, we identified Wistar rats as resilient or susceptible to SDS. Susceptible animals showed increased depressive-like behaviors with resting tachycardia and decreased heart rate variability (HRV) due to increased sympathetic tone in the heart and a less effective baroreflex. In contrast, resilient rats were protected from these alterations by increased vagal tone, resulting in greater HRV values. To our knowledge, our study is the first to indicate that harmful cardiovascular outcomes are related to depressive-like behaviors in susceptible rats and to suggest a mechanism by which resilient rats are protected from these changes. Also, our results suggest that enhanced HRV and vagal tone may be an important trait in resilient individuals.

Cardiovascular Reactivity to a Novel Stressor: Differences on Susceptible and Resilient Rats to Social Defeat Stress

“…Nevertheless, the present findings are in line with previous evidence that rats identified as susceptible or resilient to SDS based on the latency to assume a submissive posture during a defeat episode did not show differences in corticosterone release during restraint stress exposure (Wood et al, 2010). Regarding our previous study (Morais-Silva et al, 2019), differences in the experimental timeline could explain the discrepancy between the two studies. In this study, we collected the plasma for corticosterone measurement 48 h after the cannulation surgery and compared it with 24 h in the previous study.…”

“…(Isingrini et al, 2010). A recent study from our lab also showed that susceptible rats to SDS presented increased coat state deterioration (Morais-Silva et al, 2019).…”

“…In our lab, we developed a modified protocol of SDS exposure followed by the SIT, which allowed the study of different coping phenotypes to SDS in rats. Susceptible rats identified by this protocol showed social avoidance to an unknown and non-aggressive conspecific, increased coat state deterioration during SDS exposure, and an increase in immobility during the forced swim test ( Morais-Silva et al, 2019 ). These behavioral changes were followed by cardiovascular alterations, such as increased sympathetic activity and impaired baroreflex effectiveness during rest that, in turn, lead to decreased HR variability and resting tachycardia ( Morais-Silva et al, 2019 ).…”

“…Susceptible rats identified by this protocol showed social avoidance to an unknown and non-aggressive conspecific, increased coat state deterioration during SDS exposure, and an increase in immobility during the forced swim test ( Morais-Silva et al, 2019 ). These behavioral changes were followed by cardiovascular alterations, such as increased sympathetic activity and impaired baroreflex effectiveness during rest that, in turn, lead to decreased HR variability and resting tachycardia ( Morais-Silva et al, 2019 ). Despite these pieces of evidence, it is not elucidated yet how the cardiovascular system of susceptible and resilient phenotypes responds to a new stressor after CSDS.…”

Psychosocial Stress Hastens Disease Progression and Sudden Death in Mice with Arrhythmogenic Cardiomyopathy

“…As such, we used the RI paradigm in Dsg2 mut/mut mice. The RI test has been extensively employed to study cardiac alterations in response to PSS in WT healthy rodents [39][40][41][42]. First, we show that despite the profound structural and functional cardiac alterations harbored, Dsg2 mut/mut mice behave and display anxiety levels similar to their WT counterparts when unstressed.…”