Emotional remodeling with oxytocin durably rescues trauma-induced behavioral and neuro-morphological changes in rats: a promising treatment for PTSD.

ABSTRACT

Recent evidence indicates that reactivated memories are malleable and can integrate new information upon their reactivation. We injected rats with oxytocin to investigate whether the delivery of a drug which dampens anxiety and fear before the reactivation of trauma memory decreases the emotional load of the original representation and durably alleviates PTSD-like symptoms. Rats exposed to the single prolonged stress (SPS) model of PTSD were classified 15 and 17 days later as either resilient or vulnerable to trauma on the basis of their anxiety and arousal scores. Following 2 other weeks, they received an intracerebral infusion of oxytocin (0.1 µg/1 µL) or saline 40 min before their trauma memory was reactivated by exposure to SPS reminders. PTSD-like symptoms and reactivity to PTSD-related cues were examined 3-14 days after oxytocin treatment. Results showed that vulnerable rats treated with saline exhibited a robust PTSD syndrome including increased anxiety and decreased arousal, as well as intense fear reactions to SPS sensory and contextual cues. Exposure to a combination of those cues resulted in c-fos hypo-activation and dendritic arbor retraction in prefrontal cortex and amygdala neurons, relative to resilient rats. Remarkably, 83% of vulnerable rats subjected to oxytocin-based emotional remodeling exhibited a resilient phenotype, and SPS-induced morphological alterations in prelimbic cortex and basolateral amygdala were eliminated. Our findings emphasize the translational potential of the present oxytocin-based emotional remodeling protocol which, when administered even long after the trauma, produces deep re-processing of traumatic memories and durable attenuation of the PTSD symptomatology.