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

This opinion article (2021) postulates that ketamine and psychedelics substances enact their rapid fast-acting antidepressant effects by means of promoting neuroplasticity in a heterogeneous manner, by enhancing or suppressing dendritic excitability across different parts of the cellular membrane. Although precise measurements of this pharmacological effect across the entire dendritic tree are currently still lacking, the authors hypothesize that the spatial mismatches in the opposing effects of these drugs drive neuroplasticity at specific dendritic hotspots, depending on the microcircuitry of their respective target neurons.


Review: Ketamine can relieve symptoms of depression and anxiety, therefore filling a critically unmet psychiatric need. A few small-scale clinical studies suggest serotonergic psychedelics may have similar therapeutic effects. Ketamine may both enhance and suppress dendritic excitability, through microcircuit interactions involving disinhibition. Serotonergic psychedelics may both enhance and suppress excitability, through targeting coexpressed receptors. Spatial mismatch in the opposing drug actions on dendritic excitability is predicted to steer plasticity actions towards certain synapses and cell types. We present a dendrite-focused framework as a novel lens to view the actions of ketamine and serotonergic psychedelics on cortical circuits.”

Authors: Neil K. Savalia, Ling-Xiao Shao & Alex C. Kwan

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


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Published in
Trends in Neuroscience
April 1, 2021
3 citations

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