Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
17 02 2023
17 02 2023
Historique:
pmc-release:
17
02
2024
entrez:
16
2
2023
pubmed:
17
2
2023
medline:
22
2
2023
Statut:
ppublish
Résumé
Decreased dendritic spine density in the cortex is a hallmark of several neuropsychiatric diseases, and the ability to promote cortical neuron growth has been hypothesized to underlie the rapid and sustained therapeutic effects of psychedelics. Activation of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) is essential for psychedelic-induced cortical plasticity, but it is currently unclear why some 5-HT2AR agonists promote neuroplasticity, whereas others do not. We used molecular and genetic tools to demonstrate that intracellular 5-HT2ARs mediate the plasticity-promoting properties of psychedelics; these results explain why serotonin does not engage similar plasticity mechanisms. This work emphasizes the role of location bias in 5-HT2AR signaling, identifies intracellular 5-HT2ARs as a therapeutic target, and raises the intriguing possibility that serotonin might not be the endogenous ligand for intracellular 5-HT2ARs in the cortex.
Identifiants
pubmed: 36795823
doi: 10.1126/science.adf0435
pmc: PMC10108900
mid: NIHMS1882189
doi:
Substances chimiques
Hallucinogens
0
Serotonin
333DO1RDJY
Serotonin 5-HT2 Receptor Agonists
0
Receptor, Serotonin, 5-HT2A
0
Antidepressive Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
700-706Subventions
Organisme : NIMH NIH HHS
ID : R01 MH117130
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM133421
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM128997
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103526
Pays : United States
Organisme : NIH HHS
ID : S10 OD025271
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS120820
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM099608
Pays : United States
Organisme : NIH HHS
ID : S10 OD019980
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101214
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM113770
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH112507
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD079125
Pays : United States
Commentaires et corrections
Type : CommentIn
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