The pathways that activate HPA and sympatho-adrenal responses to stressors overlap extensively with pathways that orchestrate fear and other behavioral responses to threat. Nonetheless, behavioral and cardiac reactions to threat (i.e. fear grimaces, freezing, distress vocalization, elevated heart rates) can be elicited under conditions that do not increase adrenocortical or adrenomedullary activity. For this reason, although the threat-response and stress-response systems have numerous interconnections, we choose to treat them as separate, but interconnecting systems (see Figure 1). Their inter-connections are reflected in the importance of CRH in both. CRH, critical in regulating activity of the HPA axis, is also synthesized and secreted in extra-hypothalamic sites. Extra-hypothalamic CRH is involved in coordinating neuroendocrine, autonomic, and behavioral responses to threat (Brunson et al., 2001; Gray and Bingaman, 1996; Nemeroff, 1996). These defensive actions are partially orchestrated via CRH type 1 (CRH-1) receptors that are widely expressed in threat-transducing (i.e. fear) pathways and in systems that activate counter-regulatory activity (e.g., autonomic nervous system; Bale and Vale, 2004). Importantly, extra-hypothalamic CRH is produced largely by CRH-producing neurons in the central nucleus of the amygdala
