Social fear memory as a framework for understanding social defeat stress and psychopathology

Social defeat is a potent stressor in both rodents and humans that, under conditions of chronic or severe stress, can lead to persistent social avoidance. This review synthesizes evidence supporting the view that social defeat promotes the formation of social fear memory through associative learning mechanisms that parallel classical fear conditioning. Drawing on preclinical models, we describe how the context of social defeat functions as a conditioned stimulus, while the experience of defeat serves as an unconditioned stimulus, giving rise to fear-related behaviors such as freezing and social avoidance. The consolidation and expression of social fear memory rely on distributed neural circuits that integrate threat appraisal, contextual processing, and social information. These include canonical fear-related regions such as the amygdala and medial prefrontal cortex, as well as socially specialized structures, including the nucleus accumbens. These circuits are further modulated by neuroendocrine systems, including stress hormones, norepinephrine, oxytocin, vasopressin, and orexin, which shape fear memory processes in a context-dependent manner. Finally, we discuss how conceptualizing social defeat-induced learning as social fear memory provides a mechanistic framework for understanding social stress-related psychopathology and identifying targets for intervention across phases of fear memory processing, from acquisition to extinction. This perspective may inform the refinement of pharmacological and psychological treatments for stress-related disorders with a social component.