A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics.

Trends Neurosci

Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06511, USA. Electronic address:

Published: April 2021

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Article Abstract

Pilot studies have hinted that serotonergic psychedelics such as psilocybin may relieve depression, and could possibly do so by promoting neural plasticity. Intriguingly, another psychotomimetic compound, ketamine, is a fast-acting antidepressant and induces synapse formation. The similarities in behavioral and neural effects have been puzzling because the compounds target distinct molecular receptors in the brain. In this opinion article, we develop a conceptual framework that suggests the actions of ketamine and serotonergic psychedelics may converge at the dendrites, to both enhance and suppress membrane excitability. We speculate that mismatches in the opposing actions on dendritic excitability may relate to these compounds' cell-type and region selectivity, their moderate range of effects and toxicity, and their plasticity-promoting capacities.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990695PMC
http://dx.doi.org/10.1016/j.tins.2020.11.008DOI Listing

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