Effects of oxytocin on prosocial behavior and the associated profiles of oxytocinergic and corticotropin-releasing hormone receptors in a rodent model of posttraumatic stress disorder

Abstract

Background: Traumatic experience may lead to various psychological sequelae including the unforgettable trauma-associated memory as seen in posttraumatic stress disorder (PTSD), with a mechanism of impaired fear extinction due to biological imbalance among hypothalamic-pituitary-adrenal (HPA) axis and fear circuit areas such as medial prefrontal cortex (mPFC), hippocampus, and amygdala. Recently the impaired sociability seen in PTSD patients received great attention and the involvement of oxytocin (OXT) mediation is worth being investigated. This study examined whether the trauma-altered prosocial behavior can be modulated by OXT manipulation and its relationship with corticotropin-releasing hormone (CRH) signaling. Methods: Male rats previously exposed to a single prolonged stress (SPS) were evaluated for their performance in social choice test (SCT) and novel object recognition test (NORT) following the introduction of intranasal oxytocin (OXT) and OXT receptor antagonist atosiban (ASB). OXT receptors (OXTR) and CRH receptors (CRHR1, CRHR2) were quantified in both protein and mRNA levels in medial prefrontal cortex (mPFC), hippocampus, and amygdala. Results: SPS reduced inclination of rats staying at the sociable place with performing less prosocial contacts. OXT can amend the deficit but this effect was blocked by ASB. Expression of OXTR became reduced following SPS in mPFC and amygdala, the latter exhibited higher therapeutic specificity to OXT. Expression of CRHR1 appeared more sensitive than CRHR2 to SPS, higher CRHR1 protein levels were found in mPFC and amygdala. Conclusion: Psychological trauma-impaired sociability is highly associated with OXT signaling pathway. Intranasal OXT restored both the SPS-impaired prosocial contacts and the SPS-reduced OXTR expressions in mPFC and amygdala. OXT may have therapeutic potential to treat PTSD patients with impaired social behaviors.