Neurobiological mechanisms supporting experience-dependent resistance to social stress

Highlights

• Stress resilience is an active process that involves distinct neural circuits.

• Experience-dependent neural plasticity in key brain regions supports resilience.

• Dominant hamsters show resistance to the effects of social defeat.

• Neural plasticity in vmPFC circuits supports stress resistance in dominant hamsters.

Abstract

Humans and other animals show a remarkable capacity for resilience following traumatic, stressful events. Resilience is thought to be an active process related to coping with stress, although the cellular and molecular mechanisms that support active coping and stress resistance remain poorly understood. In this review, we focus on the neurobiological mechanisms by which environmental and social experiences promote stress resistance. In male Syrian hamsters, exposure to a brief social defeat stressor leads to increased avoidance of novel opponents, which we call conditioned defeat. Also, hamsters that have achieved dominant social status show reduced conditioned defeat as well as cellular and molecular changes in the neural circuits controlling the conditioned defeat response. We propose that experience-dependent neural plasticity occurs in the prelimbic (PL) cortex, infralimbic (IL) cortex, and ventral medial amygdala (vMeA) during the maintenance of dominance relationships, and that adaptations in these neural circuits support stress resistance in dominant individuals. Overall, behavioral treatments that promote success in competitive interactions may represent valuable interventions for instilling resilience.

Introduction

Stressors often generate adaptive behavioral and physiological responses that restore internal homeostasis. However, when stressors are perceived as uncontrollable, prolonged, or especially severe, they can lead to several negative health consequences, including major depression, panic disorder, and post-traumatic stress disorder (PTSD) (Abelson et al., 2007, Meewisse et al., 2007, Heim et al., 2008). Only a portion of individuals exposed to stressful life events develop stress-related psychopathology, suggesting that a great deal of individual variation exists in vulnerability to the negative consequences of stress. More than two-thirds of people in the general population experience a traumatic event at some point in their lifetime, but only 10–20% develop PTSD (Galea et al., 2005, Thomas et al., 2010). Similarly, only 20–25% of individuals exposed to major stressful events develop major depression (Cohen et al., 2007). Understanding the neural circuits and cellular mechanisms that control stress vulnerability is an important step toward identifying novel targets for the prevention and treatment of stress-related psychopathology.

Resilience refers to an individual’s capacity to cope with stress and adversity so that they avoid the negative psychological and biological consequences that would otherwise impair physical and psychological well-being (Luthar et al., 2006). Resilience may be demonstrated by resistance to the negative effects of stress or by recovery to a normal state of functioning more quickly than expected following traumatic stress. It is important to distinguish between resistance to and recovery from stressful events, as these processes might involve separate brain regions, neurochemicals, and identifying biomarkers (Yehuda et al., 2006). In animal models, the distinction is not always clear, and resilience usually refers to a decrease in stress-induced changes in future behavior. This body of work indicates that resilience is not simply a passive response involving a failure to display the neuroendocrine, cellular, and molecular changes characteristic of susceptible individuals, but is also an active response that involves distinct neural circuits and cellular mechanisms (Russo et al., 2012).

In this review, we focus on neurobiological mechanisms controlling active processes that characterize resilient individuals. Several animal models of stress resilience focus on mechanisms underlying individual differences that are likely related to genetic and epigenetic factors. We briefly review literature on individual differences in stress vulnerability, although several excellent reviews have recently addressed this topic (Coppens et al., 2010, Russo et al., 2012, Wu et al., 2013). Here, we instead emphasize animal models that investigate mechanisms controlling experience-dependent forms of stress resistance with a focus on resistance to social defeat in Syrian hamsters. In cases of experience-dependent stress resilience, individuals exposed to specific environmental or social stimuli show a reduction in the effects of stress. We maintain that understanding the neurobiological mechanisms controlling the development of resilience should provide the foundation for future evidence-based interventions targeting those at risk of stress-related psychopathology.