Rethinking the role of TRKB in the action of antidepressants and psychedelics.
Trends in neurosciences November 1, 2024 Cecilia Anna Brunello, Cecilia Cannarozzo, Eero Castrén 29 citations
Antidepressant drugs, including slow-acting types, fast-acting ketamine, and psychedelics, all promote neuronal plasticity through activation of BDNF signaling via its receptor TRKB, though each drug targets different cells. The authors propose that some antidepressants may directly bind to TRKB and allosterically enhance BDNF signaling. Activating TRKB in parvalbumin-containing interneurons disinhibits cortical networks and reopens a juvenile-like window of plasticity. This rewiring of faulty neural circuits, combined with environmental input, may explain clinical antidepressant effects. This hypothesis could guide development of new treatments.