Animal studies tracking the adaptation/pathology transition are difficult to design, due to the lack of accompanying self-reports signifying emotional or physical discomfort characteristic of human stress-related disorders. We have attempted to address this issue by comparing neural activity in habituating (repeated restraint) vs. non-habituating (CVS) models, as the latter exhibits a more severe HPA axis “phenotype,” in terms of baseline corticosterone secretion, adrenal hypertrophy and thymic involution (Flak et al., 2012). The CVS regimen also induces behavioral changes suggestive of altered cognition (increased immobility in the forced swim test) and hedonic processing (decreased sucrose preference) (Ulrich-Lai et al., 2007; Jankord et al., 2011). Using FosB staining as a marker of long-term activation, we demonstrated that both repeated restraint and CVS procedures increase the number of activated neurons in key stress regulatory areas, including the ventral medial prefrontal cortex and the dorsomedial hypothalamus, the latter a structure linked to integration of endocrine, autonomic and behavioral stress responses. However, exposure to CVS caused FosB activation in regions not affected by repeated restraint, including the posterior hypothalamus and the NTS, both of which
