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.