Fluoxetine and Ketamine Enhance Extinction Memory and Brain Plasticity by Triggering the p75 Neurotrophin Receptor Proteolytic Pathway.
Biological psychiatry February 1, 2025 Cassiano Ricardo Alves Faria Diniz, Ana Paula Crestani, Plinio Cabrera Casarotto et al. 15 citations
Antidepressants such as fluoxetine and ketamine bind to the p75 neurotrophin receptor (p75NTR) and trigger its proteolysis by α- and γ-secretase, leading to p75NTR nuclear localization. These drugs also enhance brain plasticity and extinction memory in mice and rats, and these effects depend on p75NTR signaling. The authors propose that antidepressants co-opt both the BDNF/TrkB and proBDNF/p75NTR systems to promote activity-dependent synaptic competition and brain remodeling.