“Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors” (2023), by Maxemiliano V. Vargas et al. Psychology research paper. Original abstract below, unchanged. A free PDF is available.

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

Maxemiliano V. Vargas, Lee E. Dunlap, Chunyang Dong et al. · February 16, 2023 · Psychology

Abstract

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.

Free PDF DOI: 10.1126/science.adf0435