Abstract

While social stress exposure is a common risk factor for affective disorders, most individuals exposed to it can maintain normal physical and psychological functioning. However, factors that determine susceptibility vs. resilience to social stress remain unclear. Here, the resident-intruder model of social defeat was used as a social stressor in male C57BL/6J mice to investigate the difference between susceptibility and resilience. As depression is often characterized by hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, we conducted the present study to further investigate the individual differences in the HPA axis response and glucocorticoid receptor (GR) protein expression and translocation between susceptible mice and resilient mice. We found that hypercortisolemia, induced by social defeat stress occurred in susceptible mice, but not in resilient mice. Moreover, susceptible mice exhibited significantly less GR protein expression and nuclear translocation in the hippocampus than resilient mice. Treatment with escitalopram could decrease the serum corticosterone (CORT), increase GR protein expression as well as nuclear translocation in the hippocampus and ultimately reverse social withdrawal behaviors in susceptible mice. These results indicate that the up-regulation of GR and the enhancement of GR nuclear translocation in the hippocampus play an important role in resilience to chronic social defeat stress.

Highlights

  • Depression is a public health concern associated with high morbidity and mortality (Silva et al, 2014)

  • Even though the corticotropin-releasing factor (Crf) mRNA expression of susceptible mice subsided 4 weeks after the last social defeat stress, the serum CORT in this group still remained at a high level

  • Increased basal corticosterone levels following chronic stress exposure have been reported in many studies (Sapolsky, 1992; Bartolomucci et al, 2005; Keeney et al, 2006; Schmidt et al, 2007)

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Summary

Introduction

Depression is a public health concern associated with high morbidity and mortality (Silva et al, 2014). Chronic social stress results in serious effects (Fuchs and Flugge, 2002) such as a robust depression-like phenotype marked by passive defense postures, social-avoidance behaviors, anhedonia, anxiety (Kudryavtseva et al, 1991; Rygula et al, 2005), and cognitive dysfunction (Yu et al, 2011). Antidepressants can counteract these depressivelike symptoms (Berton et al, 2006; Rygula et al, 2006a,b). These studies reveal that the disturbance of the HPA axis response and GR protein expression and translocation may relevantly correlate with some of the pathological abnormalities observed in depression

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