Rapid Acting Antidepressants in Chronic Stress Models: Molecular and Cellular Mechanisms
Brendan Hare, Sriparna Ghosal, Ronald S. Duman
Chronic Stress February 1, 2017 DOI: 10.1177/2470547017697317 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Anxiety |
| Keywords | Antidepressant Monoamine oxidase Prefrontal cortex Social defeat Depression economics Chronic stress Psychopharmacology Psychotomimetic Nmda receptor Cognition |
| Citations | 69 |
| Key findings | Rapid-acting antidepressants like ketamine can reverse stress-associated morphological and behavioral changes in rodent models, and ongoing research aims to identify their molecular, cellular, and circuit-level targets. |
Abstract
Stress-associated disorders, including depression and anxiety, impact nearly 20% of individuals in the United States. The social, health, and economic burden imposed by stress-associated disorders requires in depth research efforts to identify suitable treatment strategies. Traditional medications (e.g., selective serotonin reuptake inhibitors, monoamine oxidase inhibitors) have significant limitations, notably a time lag for therapeutic response that is compounded by low rates of efficacy. Excitement over ketamine, a rapid acting antidepressant effective in treatment resistant patients, is tempered by transient dissociative and psychotomimetic effects, as well as abuse potential. Rodent stress models are commonly used to produce behavioral abnormalities that resemble those observed in stress-associated disorders. Stress models also produce molecular and cellular morphological changes in stress sensitive brain regions, including the prefrontal cortex and hippocampus that resemble alterations observed in depression. Rapid acting antidepressants such as ketamine can rescue stress-associated morphological and behavioral changes in rodent models. Here, we review the literature supporting a role for rapid acting antidepressants in opposing the effects of stress, and summarize research efforts seeking to elucidate the molecular, cellular, and circuit level targets of these agents.
Comparable studies
Other narrative reviews on anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Mindfulness-based interventions: an overall review General (healthcare, schools, workplace) | 2021 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review | |
| Mindfulness Meditation and Psychopathology | 2018 | Review | |
| Management of Treatment-Resistant Depression: Challenges and Strategies | 2020 | Review |
Citations in the library
Cited by 16
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Molecular Pharmacology and Neurobiology of Rapid-Acting Antidepressants The Annual Review of Pharmacology and Toxicology October 9, 2018
- Neurobiological Mechanisms of Ketamine: Depression, Suicide, Trauma, and Chronic Stress Pathologies Psychiatric Annals February 1, 2020
- A Narrative Review: The Role that Ketamine May Play in the Treatment of Depression and the Underlying Mechanisms of Its Effect BILT Student Research Journal 2025 - Issue 6 July 1, 2025
- A Robust and Reproducible Connectome Fingerprint of Ketamine is Highly Associated with the Connectomic Signature of Antidepressants medRxiv Preprint Server April 10, 2020
and 11 more in the library
Cites 17
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- 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
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
and 12 more in the library