Examining the Role of Oxytocinergic Signaling and Neuroinflammatory Markers in the Therapeutic Effects of MDMA in a Rat Model for PTSD.

MDMA treatment facilitated fear extinction and reduced shock-induced freezing and social deficits in a rat model of PTSD. Shock exposure altered oxytocin receptor gene expression and caused neuroinflammation in the medial prefrontal cortex and basolateral amygdala, which MDMA restored. An oxytocin receptor antagonist blocked MDMA's effects on extinction and freezing, indicating that oxytocinergic signaling mediates these therapeutic actions.

Study at a glance

Abstract

MDMA-assisted psychotherapy has shown potential as an effective treatment for post-traumatic stress disorder (PTSD). Preclinical studies involving rodents have demonstrated that MDMA can facilitate the extinction of fear memories. It has been noted that MDMA impacts oxytocin neurons and pro-inflammatory cytokines. Thus, the aim of this study was to explore the role of oxytocinergic signaling and neuroinflammatory markers in the therapeutic effects of MDMA. To achieve this, male rats were subjected to a model of PTSD involving exposure to shock and situational reminders. MDMA was microinjected into the medial prefrontal cortex (mPFC) before extinction training, followed by behavioral tests assessing activity levels, anxiety, and social function. Our findings indicate that MDMA treatment facilitated fear extinction and mitigated the shock-induced increase in freezing, as well as deficits in social behavior. Shock exposure led to altered expression of the gene coding for OXT-R and neuroinflammation in the mPFC and basolateral amygdala (BLA), which were restored by MDMA treatment. Importantly, the OXT-R antagonist L-368,899 prevented MDMA's therapeutic effects on extinction and freezing behavior. In conclusion, MDMA's therapeutic effects in the PTSD model are associated with alterations in OXT-R expression and neuroinflammation, and MDMA's effects on extinction and anxiety may be mediated by oxytocinergic signaling.