Neurobiological mechanism of a new pharmacological candidate to be combined with behavioral therapy for treating post-traumatic stress disorder: BDNF-TrkB signaling and fear extinction

Abstract

Evidence-based psychotherapy, such as prolonged exposure (PE) or cognitive processing therapy, is the first-line therapy for post-traumatic stress disorder (PTSD). However, patients with PTSD often drop out from those psychotherapies. To prevent dropout, combining these psychotherapies with pharmacotherapy may be useful. Understanding the underlying neurobiological mechanisms of drug action is necessary for proper pharmacotherapy. It has been reported that brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) are involved in the enhancement of fear extinction, which is considered a basic theoretical model for PE across species. Recently, a selective TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), that can pass through the blood-brain barrier has been developed. Therefore, this review summarizes the role of BDNF-TrkB signaling in fear extinction and drugs targeting BDNF-TrkB signaling.