Glucocorticoid Abnormalities in Female Rats Exposed to a Predator-Based Psychosocial Stress Model of PTSD

People with post-traumatic stress disorder (PTSD) exhibit heightened anxiety and enhanced negative feedback of the hypothalamus-pituitary-adrenal (HPA) axis. We previously reported that male rats exposed to a predator-based psychosocial stress model of PTSD exhibited comparable changes in anxiety-like behavior and HPA axis activity, including lower baseline levels of corticosterone and a greater suppression of corticosterone after dexamethasone administration. Here, we assessed whether we would observe similar effects 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 combination with chronic social instability. Three weeks after the second cat exposure, we assessed anxiety-like behavior on an elevated plus maze (EPM) and collected blood samples from rats in the absence or presence of dexamethasone to quantify serum corticosterone levels. Although stressed females did not display heightened anxiety on the EPM, they exhibited significantly lower overall corticosterone levels and a greater suppression of corticosterone after dexamethasone administration. The observation of significantly lower overall corticosterone levels in stressed females was replicated in a separate, independent experiment. These findings suggest that the predator-based psychosocial stress model of PTSD may be useful for studying mechanisms that underlie changes in HPA axis function in females exposed to trauma

Impact of Ketamine on Physiological and Behavioral Sequelae Induced by a Predator-Based Psychosocial Stress Model of PTSD

Few pharmacological agents effectively treat the array of symptoms involved in post-traumatic stress disorder (PTSD). SSRIs are the most commonly prescribed medication for PTSD, but they lead to remission rates of barely 50% and take weeks to months before producing symptom relief. Therefore, we examined the impact of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist that has rapid antidepressant effects, on PTSD-like symptom development in rats exposed to a predator-based psychosocial stress model of PTSD. Male and female Sprague-Dawley rats were exposed to psychosocial stress for 31 days. The psychosocial stress procedure involved two separate cat exposures and daily social instability. Immediately after the first cat exposure, rats were given intraperitoneal injections of ketamine (15 mg/kg) or vehicle. Three weeks following the second cat exposure, the rats were tested for symptoms of anxiety-like behavior on an elevated plus maze and in an open field; we also assessed rats’ hyperarousal by examining their baseline startle responses. Data collection is still in progress, but preliminary results suggest that ketamine reduced anxiety on the EPM and in the open field in psychosocially stressed males. These and the ensuing results in females will be discussed

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

Impact of Alcohol on the Development of PTSD-Like Sequelae following Intense Stress

Traumatic events are frequently accompanied by alcohol use, and although some research has shown that alcohol increases intrusive memory formation in healthy subjects, limited work has examined the impact of alcohol on the development of post-traumatic stress disorder (PTSD). Moreover, there has been no work experimentally testing the influence of alcohol on PTSD-like symptoms in animal models. Thus, we examined the effects of alcohol on the development of PTSD-like symptoms in rats exposed to a predator-based model of traumatic stress. Male and female Sprague-Dawley rats were given intraperitoneal injections of alcohol (1.5 g/kg) or vehicle (water) 30 minutes before being exposed to an adult, female cat for 1 hr. One week later, the rats were tested for symptoms of anxiety-like behavior on an elevated plus maze and in an open field. We also assessed rats’ hyperarousal by examining their baseline startle responses. According to the results, males, but not females, that were treated with alcohol prior to stress displayed significantly greater anxiety and larger startle responses than rats treated with vehicle before stress. These findings suggest that peri-traumatic alcohol ingestion could increase the risk of developing PTSD, at least in males