Prolonged epigenomic and synaptic plasticity alterations following single exposure to a psychedelic in mice.
Cell Rep
; 37(3): 109836, 2021 10 19.
Article
em En
| MEDLINE
| ID: mdl-34686347
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.
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Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Receptor 5-HT2A de Serotonina
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Epigênese Genética
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Espinhas Dendríticas
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Agonistas do Receptor 5-HT2 de Serotonina
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Lobo Frontal
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Epigenoma
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Alucinógenos
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Anfetaminas
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Plasticidade Neuronal
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article