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

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…

• NS
  National Science Foundation

  Award: CHE-04-43516
• CA
  Camille and Henry Dreyfus Foundation
• MI
  MIND Institute, University of California, Davis

  Awards: HD079125, U54 HD079125
• NI
  National Institutes of Health

  Awards: T32GM099608, R01GM128997, U54 HD079125, 08P0ES 05707C, U01NS120820, 1S10OD025271, 1S10OD025271-01A1, T32MH112507, T32GM113770, R35GM133421, 1S10OD019980-01A1
• UO
  University of California, Davis

  Award: U54 HD079125
• NI
  National Institute on Drug Abuse
• DO
  Division of Chemistry