A neuroendocrine mechanism for sustaining fear.

Fear is an adaptive response to recognition of a potentially dangerous event. Glucocorticoids are essential for maintaining a wide variety of behavioral events by their regulation of numerous genes; one such gene encodes corticotrophin-releasing hormone (CRH). CRH is involved in diverse behavioral responses to changing environmental demands. In this review, we focus on one aspect of glucocorticoid regulation of CRH--namely, fear-related responses to diverse classes of adverse events, such as those represented by contextual and cue-specific stimuli. Three extra-hypothalamic forebrain sites appear crucial for fear-related behavioral responses: the amygdala and the bed nucleus of the stria terminalis for sustaining adaptive fear-related behaviors, and the medial prefrontal cortex for modulating fear-related behaviors. Central regulation of CRH by glucocorticoids is important for adaptive and sustained fear-related behaviors, and its aberration is associated with anxiety and depressive disorders.