Stimulation of the HPA axis occurs in reaction to or in anticipation of stress (Herman et al., 2003; Ulrich-Lai and Herman, 2009). Physiological threats (systemic stressors) initiate largely reflexive responses that can be triggered without conscious perception. However, anticipation of threat requires the organism to interpret the significance of multi-modal sensory information with respect to previous experience. Thus, stimuli that predict adversity (psychogenic stressors) can generate an HPA axis response in the absence of an existing physiologic insult. The relevance of the anticipatory glucocorticoid response hinges on the predicted need for adaptive hormonal secretion in order to redistribute resources (e.g., energy) to meet the challenge (Herman et al., 2003; Ulrich-Lai and Herman, 2009). Appropriate activation of the HPA axis by acute stress is critical, as inappropriately low reactivity can hinder physiological resilience and cognitive processes (e.g., learning and memory) (Diamond et al., 1992; Reber et al., 2007). However, many of the effects of glucocorticoids that are beneficial for short-term survival can be counterproductive or even deleterious if prolonged. Therefore, the activation and inhibition of glucocorticoid release is a temporally regulated process involving rapid neuronal activation and efficient inhibition.
