Enhanced Negative Feedback of the HPA Axis and Increased Noradrenergic Activity in Females Exposed to a Predator-Based Psychosocial Stress Model of PTSD

People with post-traumatic stress disorder (PTSD) exhibit numerous physiological alterations, including lower baseline cortisol levels, enhanced negative feedback of the hypothalamus-pituitary-adrenal (HPA) axis, increased noradrenergic activity, and reduced serotonergic activity. Male rats exposed to a predator-based psychosocial stress model of PTSD exhibit similar changes in HPA axis function and neurotransmission. Here, we examined whether similar effects would be observed in female rats exposed to this model. Adult female Sprague-Dawley rats were exposed to a cat on two occasions, separated by 10 days, in conjunction with daily social instability. Three weeks following the second cat exposure, we examined rats’ anxiety-like behavior on an elevated plus maze (EPM), collected blood samples at baseline and following dexamethasone administration to quantify corticosterone levels, and extracted brains to quantify markers of noradrenergic and serotonergic activity in the hippocampus and prefrontal cortex (PFC). Stressed females did not exhibit heightened anxiety on the EPM, but, relative to controls, they displayed lower corticosterone levels and a greater suppression of corticosterone following dexamethasone administration. Stressed females also exhibited increased markers of noradrenergic activity in the dorsal hippocampus and PFC. These findings suggest that this model of PTSD may be useful for studying mechanisms underlying trauma-induced changes in female physiology.