Details

Autor(en) / Beteiligte

• Vargas, Maxemiliano V
• Dunlap, Lee E
• Dong, Chunyang
• Carter, Samuel J
• Tombari, Robert J
• Jami, Shekib A
• Cameron, Lindsay P
• Patel, Seona D
• Hennessey, Joseph J
• Saeger, Hannah N
• McCorvy, John D
• Gray, John A
• Tian, Lin
• Olson, David E

Titel

Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors

Ist Teil von

• Science (American Association for the Advancement of Science), 2023-02, Vol.379 (6633), p.700-706

Ort / Verlag

United States: The American Association for the Advancement of Science

Erscheinungsjahr

2023

Quelle

American Association for the Advancement of Science

Beschreibungen/Notizen

• 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.