Fast-acting antidepressant-like effects of ketamine in aged male rats.
Elena Hernández-Hernández, Sandra Ledesma-Corvi, Jordi Jornet-Plaza, M Julia García-Fuster
Pharmacological Reports October 1, 2024 DOI: 10.1007/s43440-024-00636-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | 14-month-old male rats |
| Intervention | Ketamine |
| Dose | 5 mg/kg, ip |
| Duration | 30 minutes (acute) and 7 days (repeated) |
| Topics | Ketamine Esketamine |
| Keywords | Aging Bdnf Fast-acting antidepressant Ketamine therapy Depression treatment Geriatric psychiatry Neuroscience research Brain health |
| Citations | 8 |
| Key findings | Acute ketamine induced a fast-acting antidepressant-like effect in aged rats, but repeated treatment failed to maintain efficacy and reduced mBDNF in the prefrontal cortex. |
Abstract
The aging process causes anatomical and physiological changes that predispose to the development of late-life depression while reduces the efficacy of classical antidepressants. Novel fast-acting antidepressants such as ketamine might be good candidates to be explored in the context of aging, especially given the lack of previous research on its efficacy for this age period. Thus, the aim of the present study was to characterize ketamine's effects in older rats. The fast-acting (30 min) and repeated (7 days) antidepressant-like effects of ketamine (5 mg/kg, ip) were evaluated in 14-month-old single-housed rats through the forced-swim and novelty-suppressed feeding tests. In parallel, the modulation of neurotrophic-related proteins (i.e., mBDNF, mTOR, GSK3) was assessed in brain regions affected by the aging process, prefrontal cortex and hippocampus, as well as possible changes in hippocampal cell proliferation. Acute ketamine induced a fast-acting antidepressant-like response in male aged rats, as observed by a reduced immobility in the forced-swim test, in parallel with a region-specific increase in mBDNF protein content in prefrontal cortex. However, repeated ketamine failed to induce antidepressant-like efficacy, but decreased mBDNF protein content in prefrontal cortex. The rate of hippocampal cell proliferation and/or other markers evaluated was not modulated by either paradigm of ketamine. These results complement prior data supporting a fast-acting antidepressant-like effect of ketamine in rats, to further extend its efficacy to older ages. Future studies are needed to further clarify the lack of response after the repeated treatment as well as its potential adverse effects in aging.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| 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 Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 5
- Brain-derived neurotrophic factor (BDNF) changes in rodent models of schizophrenia induced by ketamine: a systematic review. Naunyn-Schmiedeberg's Archives of Pharmacology February 20, 2025
- Psilocybin as a fast-acting and long-lasting antidepressant for adolescence: Proposing NeuroD1 as a biomarker of its long-term plasticity Biomedicine & Pharmacotherapy October 30, 2025
- Characterizing psilocybin as an antidepressant for adolescence in male and female rats bioRxiv (Cold Spring Harbor Laboratory) December 22, 2024
- Exploratory non-randomized clinical trial of subcutaneous esketamine in treatment-resistant depression: Effects of ketamine-assisted psychotherapy Journal of Affective Disorders August 10, 2026
- Preliminary Non-Randomized Clinical Trial of Subcutaneous Esketamine in Treatment-Resistant Depression: Exploring Adjunctive Effects of Ketamine-Assisted Psychotherapy medRxiv Preprint Server May 31, 2026
Cites 23
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
- BDNF Release Is Required for the Behavioral Actions of Ketamine The International Journal of Neuropsychopharmacology October 31, 2014
- Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression ACS Chemical Neuroscience March 5, 2020
and 18 more in the library