| First Author | Vargas MV | Year | 2023 |
| Journal | Science | Volume | 379 |
| Issue | 6633 | Pages | 700-706 |
| PubMed ID | 36795823 | Mgi Jnum | J:341875 |
| Mgi Id | MGI:7442322 | Doi | 10.1126/science.adf0435 |
| Citation | Vargas MV, et al. (2023) Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors. Science 379(6633):700-706 |
| abstractText | 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. |
