In mice undergoing alcohol abstinence, treatment with ayahuasca blocked the return of alcohol self-administration. The effects depended on activation of the 5-HT2A receptor. The findings suggest that ayahuasca and other 5-HT2A receptor agonists could serve as adjunctive pharmacotherapies for alcohol use disorder.
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.