Serotonergic and glutamatergic mechanisms converge in ketamine's rapid responses.
Trends in Neurosciences May 2026 DOI: 10.1016/j.tins.2026.03.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Commentary Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Depression Esketamine Ketamine Serotonin |
| Keywords | Nmda receptors Vip interneurons Prefrontal cortex Rapid-acting antidepressants Serotonin transporter |
| Key points | Argues that ketamine's rapid antidepressant effects may involve converging serotonergic and glutamatergic pathways, citing Luo and colleagues' mouse findings that ketamine inhibits the serotonin transporter and that prefrontal serotonergic signaling synergizes with NMDA receptor blockade to recruit VIP interneurons and drive fast behavioral responses. |
Abstract
Ketamine's rapid antidepressant actions are commonly attributed to glutamatergic mechanisms. In a recent study, Luo and colleagues have shown that ketamine inhibits the serotonin transporter and that prefrontal serotonergic signaling synergizes with NMDA receptor blockade to recruit vasoactive intestinal peptide interneurons in mice, driving fast behavioral responses. These findings suggest convergent serotonergic and glutamatergic pathways underlying ketamine's antidepressant effects.
Citations in the library
Cites 7
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism American Journal of Psychiatry August 29, 2018
- Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability Molecular Psychiatry April 15, 2021
- Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses. Neuropsychopharmacology March 1, 2025
and 2 more in the library