Prolonged epigenetic and synaptic plasticity alterations following single exposure to a psychedelic in mice
bioRxiv (Cold Spring Harbor Laboratory) February 25, 2021 Mario de la Fuente Revenga, Bohan Zhu, Christopher A. Guevara et al. 11 citations preprint
A single dose of the psychedelic DOI produces rapid and sustained antidepressant-like effects by altering chromatin organization at enhancer regions of genes involved in synaptic assembly in the frontal cortex, an effect mediated by the 5-HT2A receptor. These epigenetic changes drive lasting synaptic plasticity and accelerate fear extinction. The findings suggest that epigenetic-driven synaptic plasticity underlies psychedelics' long-lasting antidepressant action, but also indicate potential risks for individuals with underlying vulnerability to psychosis, as the altered neuronal epigenome overlapped with genetic loci associated with schizophrenia, depression, and attention deficit hyperactivity disorder.