The CNS mechanisms regulating stress habituation appear to involve limbic forebrain circuitry. Functional studies indicate that local inactivation of the ventral PFC region prior to restraint stress blocks the development of habituation to subsequent exposure, suggesting activation is necessary for the process (Weinberg et al., 2010). The basolateral amygdala also appears essential for HPA axis habituation, as local blockade of beta-adrenergic receptors after daily stress exposure attenuates reductions in ACTH and corticosterone release observed following repeated restraint (Grissom and Bhatnagar, 2011). It is important to note that the ventral prefrontal cortex has rich connections with basolateral amygdala (McDonald et al., 1999; Vertes, 2004), and thus it is possible that the two work in concert to promote habituation. Other limbic forebrain regions may also play a role in the habituation process; for example, diminished HPA axis responses to repeated noise exposure is associated with a significant increase in c-fos mRNA activation in the orbitofrontal cortex, in contrast to decreases seen in other regions of the frontal cortex (including the PFC) (Campeau et al., 2002). Like other limbic cortices, the orbitofrontal cortex
