Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus.
Lêda S B Garcia, Clarissa M Comim, Samira S Valvassori, Gislaine Z Réus, Luciana M Barbosa, Ana Cristina Andreazza, Laura Stertz, Gabriel R Fries, Elaine Cristina Gavioli, Flávio Kapczinski, João Quevedo
Progress in Neuro-Psychopharmacology and Biological Psychiatry January 1, 2008 DOI: 10.1016/j.pnpbp.2007.07.027 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Ketamine Imipramine |
| Dose | Ketamine 5, 10, 15 mg/kg; imipramine 10, 20, 30 mg/kg |
| Duration | Acute administration |
| Measures | Forced swimming test, Open-field test, ELISA-sandwich assay |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine at 10 and 15 mg/kg and imipramine at 20 and 30 mg/kg reduced immobility time in the forced swimming test without affecting locomotion. Only ketamine at the higher dose increased hippocampal BDNF protein levels, suggesting this increase may be necessary for its rapid antidepressant action. |
Abstract
Ketamine is a non-competitive antagonist to the phencyclidine site of N-methyl-d-aspartate (NMDA) receptor. Clinical findings point to a rapid onset of action for ketamine on the treatment of major depression. Considering that classic antidepressants may take long-lasting time to exhibit their main therapeutic effects, the present study aims to compare the behavioral effects and the BDNF hippocampus levels of acute administration of ketamine and imipramine in rats. To this aim, rats were acutely treated with ketamine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and animal behavioral was assessed in the forced swimming and open-field tests. Afterwards, BDNF protein hippocampal levels were assessed in imipramine- and ketamine-treated rats by ELISA-sandwich assay. We observed that ketamine at the doses of 10 and 15 mg/kg, and imipramine at 20 and 30 mg/kg reduced immobility time compared to saline group, without affecting locomotor activity. Interesting enough, acute administration of ketamine at the higher dose, but not imipramine, increased BDNF protein levels in the rat hippocampus. In conclusion, our findings suggest that the increase of hippocampal BDNF protein levels induced by ketamine might be necessary to produce a rapid onset of antidepressant action.
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
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- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Ketamine – More mechanisms of action than just NMDA blockade Trends in Anaesthesia and Critical Care March 22, 2014
- Ketamine: 50 Years of Modulating the Mind Frontiers in Human Neuroscience November 29, 2016
- Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial The International Journal of Neuropsychopharmacology March 17, 2009
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