Understanding psychedelic antidepressant action
RESEARCH HIGHLIGHT
07 March 2023
Dysregulation of the cortex is a central feature of many neuropsychiatric disorders, including depression. Recent evidence suggests that psychedelics (such as N,N-dimethyltryptamine (DMT) and psilocin) promote cortical structural and functional neuroplasticity through activation of 5-hydroxytryptamine 2A receptors (5-HT2AR), which is thought to underlie their rapid and sustained antidepressant-like effects. In contrast, other 5-HT2AR agonists, including serotonin itself, do not promote such neuroplasticity. Here, Vargas et al. explore how the structures of 5-HT2AR ligands affect their abilities to promote neuronal growth. Increasing N-methylation of 5-HT2AR ligands enhanced their ability to promote growth of rat cortical neurons, which was greatest with N,N-dimethyl compounds. These lipophilic membrane-permeable ligands mediated their neuroplastogenic effects via intracellular 5-HT2ARs in cortical neurons, which are inaccessible to unmethylated serotonin. Inducing cellular uptake of serotonin, using electroporation or by expressing the serotonin transporter (SERT), induced structural plasticity in rat cortical neurons. Similarly, administering a serotonin-releasing agent to mice expressing SERT on cortical neurons of the medial prefrontal cortex increased dendritic spine density and produced an antidepressant-like response.
Access options
Subscription info for Chinese customers
We have a dedicated website for our Chinese customers. Please go to naturechina.com to subscribe to this journal.
Rent or buy this article
Get just this article for as long as you need it
$39.95
Prices may be subject to local taxes which are calculated during checkout
Additional access options:
doi: https://doi.org/10.1038/d41573-023-00037-5
Jobs
留言 (0)