Prolonged epigenomic and synaptic plasticity alterations following single exposure to a psychedelic in mice
| dc.contributor.author | de la Fuente Revenga, Mario | en |
| dc.contributor.author | Zhu, Bohan | en |
| dc.contributor.author | Guevara, Christopher A. | en |
| dc.contributor.author | Naler, Lynette B. | en |
| dc.contributor.author | Saunders, Justin M. | en |
| dc.contributor.author | Zhou, Zirui | en |
| dc.contributor.author | Toneatti, Rudy | en |
| dc.contributor.author | Sierra, Salvador | en |
| dc.contributor.author | Wolstenholme, Jennifer T. | en |
| dc.contributor.author | Beardsley, Patrick M. | en |
| dc.contributor.author | Huntley, George W. | en |
| dc.contributor.author | Lu, Chang | en |
| dc.contributor.author | González-Maso, Javier | en |
| dc.date.accessioned | 2021-11-19T14:04:54Z | en |
| dc.date.available | 2021-11-19T14:04:54Z | en |
| dc.date.issued | 2021-10-19 | en |
| dc.description.abstract | Clinical evidence suggests that rapid and sustained antidepressant action can be attained with a single exposure to psychedelics. However, the biological substrates and key mediators of psychedelics’ enduring action remain unknown. Here, we show that a single administration of the psychedelic DOI produces fast-acting effects on frontal cortex dendritic spine structure and acceleration of fear extinction via the 5-HT2A receptor. Additionally, a single dose of DOI leads to changes in chromatin organization, particularly at enhancer regions of genes involved in synaptic assembly that stretch for days after the psychedelic exposure. These DOI-induced alterations in the neuronal epigenome overlap with genetic loci associated with schizophrenia, depression, and attention deficit hyperactivity disorder. Together, these data support that epigenomic-driven changes in synaptic plasticity sustain psychedelics’ long-lasting antidepressant action but also warn about potential substrate overlap with genetic risks for certain psychiatric conditions. | en |
| dc.description.sponsorship | This work was supported in part by the National Institutes of Health grants R01MH084894, R01MH111940, and P30DA033934 (J.G.-M.), R01GM143940 (C.L.), R01NS107512 (G.W.H.), N01DA-17-8932, and N01DA-19-8949 (P.M.B.), P50AA022537 (J.T.W.), F30MH116550 (J.M.S), T32MH087004 (C.A.G.), and T32MH020030 (M.d.l.F.R.). | en |
| dc.description.version | Published version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.doi | https://doi.org/10.1016/j.celrep.2021.109836 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/106684 | en |
| dc.identifier.volume | 37 | en |
| dc.language.iso | en | en |
| dc.publisher | Cell Press | en |
| dc.rights | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en |
| dc.title | Prolonged epigenomic and synaptic plasticity alterations following single exposure to a psychedelic in mice | en |
| dc.title.serial | Cell Reports | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |