MDMA (ecstasy) enhances the extinction of fear memories in mice through a mechanism dependent on brain-derived neurotrophic factor (BDNF). When administered before extinction training, MDMA persistently improved long-term extinction of conditioned fear. The drug increased Fos expression in the amygdala and medial prefrontal cortex, while BDNF expression rose specifically in the amygdala after extinction training. Direct infusion of MDMA into the basolateral amygdala recapitulated the extinction enhancement, and blocking BDNF signaling abolished it. These findings suggest MDMA may be a useful adjunct to exposure-based therapies for PTSD and other anxiety disorders involving altered fear learning.
MDMA enhances the extinction of fear memories in a translational behavioral model, an effect that depends on the serotonin transporter (5-HTT) and the 5-HT2A receptor. These findings support the potential use of MDMA as an adjunct to exposure therapy for fear-related disorders and highlight important pharmacological considerations for patients who are often treated with serotonin reuptake inhibitors.