Synaptic basis of rapid antidepressant action.
Ege T Kavalali, Lisa M Monteggia
European Archives of Psychiatry and Clinical Neuroscience September 29, 2024 DOI: 10.1007/s00406-024-01898-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine Neuroplasticity |
| Keywords | Bdnf Homeostatic plasticity Spontaneous neurotransmission Spontaneous neurotransmitter release Trkb Depression treatment Ketamine therapy Neurotransmitter signaling Brain chemistry |
| Citations | 4 |
| Key findings | Ketamine's rapid antidepressant effects are mediated by synaptic plasticity mechanisms, not by neuronal circuitry alterations or neurogenesis. |
Abstract
The discovery of ketamine's rapid antidepressant action has generated intense interest in the field of neuropsychiatry. This discovery demonstrated that to alleviate the symptoms of depression, treatments do not need to elicit substantive alterations in neuronal circuitry or trigger neurogenesis, but rather drive synaptic plasticity mechanisms to compensate for the underlying pathophysiology. The possibility of a rapidly induced antidepressant effect makes therapeutic pursuit of fast-acting neuropsychiatric medications against mood disorders plausible. In the meantime, the accumulating clinical as well as preclinical observations raise critical questions on the nature of the specific synaptic plasticity events that mediate these rapid antidepressant effects. This work has triggered the current growing interest in alternative psychoactive compounds that are thought to have similar properties to ketamine and its action. This review covers our insight into these questions based on the work our group has conducted on this topic in the last decade.
Comparable studies
Other narrative reviews on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists | 2012 | Review | |
| Towards an understanding of psychedelic-induced neuroplasticity. Review of preclinical and clinical studies | 2023 | Review | |
| Buddha's Brain: Neuroplasticity and Meditation [In the Spotlight] | 2008 | Review | |
| Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics | 2021 | Review | |
| Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms | 2020 | Review |
Citations in the library
Cited by 3
- Neural signaling mechanisms in depression: bridging classical monoamine hypotheses, animal models, and emerging antidepressant strategies Frontiers in Cell and Developmental Biology March 25, 2026
- Esketamine alleviates the pain-depression dyad: insights from exploratory transcriptomic profiling and Wnt4-associated molecular alterations within the anterior cingulate cortex Frontiers in Pharmacology October 16, 2026
- Subanesthetic doses of ketamine to rats and monkeys rapidly increases radioligand binding in brain to phosphodiesterase-4, an indirect marker of cAMP. Translational Psychiatry April 21, 2026
Cites 11
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Psychedelics reopen the social reward learning critical period Nature June 14, 2023
- Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms Neuropsychopharmacology July 24, 2023
- Sustained antidepressant effect of ketamine through NMDAR trapping in the LHb Nature October 18, 2023
and 6 more in the library