A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics
Neil K. Savalia, Ling-Xiao Shao, Alex C. Kwan
Trends in Neurosciences December 21, 2020 DOI: 10.1016/j.tins.2020.11.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Neuroplasticity Psilocybin Serotonin Esketamine Ketamine |
| Keywords | Antidepressant Psychotomimetic Synapse Biological neural network Hallucinogen Nmda receptor Hippocampus |
| Citations | 110 |
| Key points | Proposes that the actions of ketamine and serotonergic psychedelics may converge at dendrites to both enhance and suppress membrane excitability. |
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.