Low Doses of Ketamine and Melatonin in Combination Produce Additive Antidepressant-like Effects in Mice
Rosa Estrada-Reyes, Daniel B Quero-Chávez, Citlali Trueta, A. Miranda, Marcela Valdés-Tovar, Salvador Alarcón-Elizalde, Julián Oikawa-Sala, Jesús Argueta, Luis A Constantino-Jonapa, Jesús Muñoz-Estrada, Margarita L Dubocovich, Gloria Benítez-King
International Journal of Molecular Sciences August 26, 2021 DOI: 10.3390/ijms22179225 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Ketamine Melatonin |
| Dose | non-effective dose of ketamine |
| Topics | Esketamine Ketamine |
| Key points | A combination of a non-effective dose of ketamine and melatonin increased neurogenesis and produced antidepressant-like effects without altering locomotor activity in mice. |
Abstract
Major depressive disorder is a disabling disease with the number of affected individuals increasing each year. Current antidepressant treatments take between three to six weeks to be effective with forty percent of patients being resistant to treatment, making it necessary to search for new antidepressant treatments. Ketamine, a phencyclidine hydrochloride derivative, given intravenously, induces a rapid antidepressant effect in humans. In mice, it causes increased neurogenesis and antidepressant-like effects. However, it also produces psychomimetic effects in humans and in rodents increases the locomotor activity. In contrast, melatonin, a hormone secreted by the pineal gland and synthesized in extrapineal sites, increases new neuron formation and causes antidepressant-like effects in adult rodents with no collateral effects. Here, we assessed the effects of a non-effective dose of ketamine in combination with melatonin (KET/MEL), both on neurogenesis as well as on the antidepressant-like effect in mice. Our results showed that KET/MEL combination increased neurogenesis and produced antidepressant-like effects without altering locomotor activity after both single and triple administration protocols. Our data strongly suggest that KET/MEL combination could be used to simultaneously promote neurogenesis, reverting neuronal atrophy and inducing antidepressant-like effects.
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 3
- Participation of Ca2+-Calmodulin-Dependent Protein Kinase II in the Antidepressant-Like Effects of Melatonin. Molecular Pharmacology August 16, 2024
- Enhanced Modulation of CaMKII in Mouse Hippocampus by an Antidepressant-like Dose of Melatonin/Ketamine Combination Cells August 1, 2025
- Antidepressant Low Doses of Ketamine and Melatonin in Combination Produce Additive Neurogenesis in Human Olfactory Neuronal Precursors. Molecules September 1, 2022
Cites 7
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- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
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- Strategies to mitigate dissociative and psychotomimetic effects of ketamine in the treatment of major depressive episodes: a narrative review The World Journal of Biological Psychiatry January 11, 2016
- Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology January 2012
and 2 more in the library