Neurocircuit mechanisms underlying generation of chronic stress-induced HPA hyperdrive remain to be determined. In general, lesions of brain regions known to be involved in inhibition or excitation of acute stress reactivity do not affect the development of HPA-relevant chronic stress symptoms. For example, lesions of the ventral subiculum exacerbate responses to acute stress, but do not affect basal glucocorticoid secretion, adrenal hypertrophy or thymic atrophy following chronic stress (Herman and Mueller, 2006). Moreover, lesions of the medial and central amygdala, putative stress excitatory regions, do not attenuate chronic stress responses (Prewitt and Herman, 1997; Solomon et al., 2010). Thus, it is not clear that regions mediating acute stress responses are required for development of chronic stress-related HPA axis dysfunction.
