Ketamine Sex- and Dose-Dependently Mitigates 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 only FDA-approved medications 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 NMDA receptor antagonist that has rapid antidepressant effects, on PTSD-like symptom development in rats. Male and female rats were exposed to psychosocial stress for 31 days. The stress procedure involved two separate cat exposures and daily social instability. Immediately after the first cat exposure, rats in the stress groups were injected with ketamine (10 mg/kg or 15 mg/kg) or vehicle (0.9% saline). Three weeks following the second cat exposure, the rats were tested for symptoms of anxiety and hyperarousal. Stressed males treated with vehicle exhibited heightened anxiety on an elevated plus maze and less activity in an open field. Stressed females treated with vehicle displayed exaggerated startle responses, as well as heightened anxiety and less activity in an open field. These effects were prevented by ketamine treatment, particularly the 10 mg/kg dose. Such findings indicate that peri-traumatic administration of a sub-anesthetic dose of ketamine can prevent the onset of PTSD-like symptoms