Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats.
Lêda S B Garcia, Clarissa M Comim, Samira S Valvassori, Gislaine Z Réus, Laura Stertz, Flávio Kapczinski, Elaine C Gavioli, João Quevedo
Progress in Neuro-Psychopharmacology and Biological Psychiatry April 30, 2009 DOI: 10.1016/j.pnpbp.2009.01.004 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Rats exposed to chronic mild stress |
| Intervention | Ketamine |
| Dose | 15 mg/kg |
| Duration | 40 days of CMS, then acute or chronic treatment |
| Measures | sweet food consumption, body weight, adrenal gland weight, corticosterone levels, ACTH levels, hippocampal BDNF protein levels |
| Topics | Esketamine Ketamine |
| Key findings | Chronic mild stress induced anhedonia, adrenal hypertrophy, reduced weight gain, and elevated corticosterone and ACTH. Acute and chronic ketamine reversed adrenal and hormonal changes and restored weight, but only repeated ketamine reversed anhedonia. Ketamine did not affect hippocampal BDNF in stressed rats. |
Abstract
Several studies have supported the idea that ionotropic glutamate N-methyl-d-aspartate receptor (NMDA) is an important player in the etiology of psychopathologies, such as anxiety disorders and major depression. Additionally, studies have shown that ketamine induces antidepressant effects in humans as well as in rodents subjected to animal models of depression. In this context, the present study was aimed to evaluate behavioral and physiological effects of acute and chronic administration of ketamine, a NMDA receptor antagonist, in rats exposed to chronic mild stress (CMS). After 40 days of CMS, rats were treated with ketamine (15 mg/kg) and sweet food consumption, body and adrenal gland weight, corticosterone and adrenocorticotropic (ACTH) hormone levels, and hippocampal BDNF protein levels were assessed. Our findings demonstrated that CMS evoked anhedonia, induced hypertrophy of adrenal gland, impaired gain of body weight and increased corticosterone and ACTH circulating levels in rats. Acute and chronic treatment with ketamine reversed the increase in adrenal gland weight, promoted regain of body weight, and normalized corticosterone and ACTH circulating levels. Repeated, but not acute, administration of ketamine reversed anhedonia-like behavior, although the treatment with ketamine per se increased sweet food consumption in non-stressed rats. Finally, acute and chronic ketamine treatment did not alter hippocampal BDNF protein levels in stressed rats. In conclusion, these findings support the idea of a putative role of NMDA receptors in mood-related symptoms, and rapid and robust effects of ketamine in reverting mainly physiological alterations induced by chronic mild stressful situations in rats.
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 48
- Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression Translational Psychiatry October 14, 2014
- Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor Molecular Psychiatry May 7, 2021
- The Role of Ketamine in Treatment-Resistant Depression: A Systematic Review Current Neuropharmacology November 12, 2014
- Neural correlates of change in major depressive disorder anhedonia following open-label ketamine Journal of Psychopharmacology February 17, 2015
- Inflammation, stress and depression: an exploration of ketamine’s therapeutic profile Drug Discovery Today February 1, 2023
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Cites 7
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Intravenous ketamine therapy in a patient with a treatment-resistant major depression Swiss Medical Weekly April 21, 2007
- Repeated intravenous ketamine therapy in a patient with treatment-resistant major depression The World Journal of Biological Psychiatry May 12, 2008
- Chronic administration of ketamine elicits antidepressant-like effects in rats without affecting hippocampal brain-derived neurotrophic factor protein levels. Basic & Clinical Pharmacology & Toxicology December 2008
- Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biological Psychiatry February 15, 2008
and 2 more in the library