Effects of Systemic Administration of Oxytocin on Contextual Fear Extinction in a Rat Model of Post-Traumatic Stress Disorder

Introduction: One of the hallmark symptoms of posttraumatic stress disorder (PTSD) is the impaired extinction of traumatic memory. Single prolonged stress (SPS) has been suggested as an animal model of PTSD, since SPS rats exhibited the impaired fear extinction. Oxytocin (OXT) has been recently suggested as a potential pharmacotherapy for treatment of PTSD. In this study, using SPS rats we investigated the effects of multiple systemic administration of OXT on contextual fear extinction. Methods: SPS was conducted in three stages: restraint for 2 h, forced swim for 20 min, and diethyl ether anesthesia, and then left undisturbed in their home cage for 7 days. In the SPS group, 7 days after SPS treatment, contextual fear conditioning was performed (on day 0), and then extinction training was performed on each of four consecutive days following fear conditioning. In the sham group, the procedures were similar except that SPS treatment was not performed. Results: During extinction trial (10 min) freezing behavior was recorded. OXT (1, 10, 100 and 1000 mu g/kg) was administrated (I.P) immediately after each extinction trial. SPS rats exhibited significant impairment of contextual fear extinction as compared with sham rats. While there was no significant difference in the freezing levels between SPS and Sham rats 24 h after the fear conditioning, the freezing levels in SPS rats were significantly higher than those in sham rats after the second extinction training. Systemic OXT delayed fear extinction in sham rats as compared with sham-saline treated animals. No effect of OXT was found in SPS rats. Discussion: These findings indicate that increasing OXT transmission during fear memory reactivation delays fear extinction, and thus, the recommendation of OXT for PTSD treatment should be considered with caution.