Effect of chronic administration of ketamine on the mitochondrial respiratory chain activity caused by chronic mild stress.
Gislaine T Rezin, Cinara L Gonçalves, Juliana F Daufenbach, Milena Carvalho-Silva, Lislaine S Borges, Julia S Vieira, Fernanda V Hermani, Clarissa M Comim, João Quevedo, Emilio L Streck
Acta Neuropsychiatrica December 2010 DOI: 10.1111/j.1601-5215.2010.00500.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adult male Wistar rats |
| Intervention | Ketamine |
| Duration | 40 days of chronic mild stress; chronic ketamine treatment |
| Topics | Esketamine Ketamine |
| Key findings | Chronic mild stress decreased sweet-food intake, increased adrenal gland weight, and prevented weight gain in rats, and inhibited mitochondrial respiratory chain complexes I, III, and IV in cerebral cortex and cerebellum. Chronic ketamine reversed the behavioral and body-weight effects and reversed complex I, III, and IV inhibition in cerebral cortex, but only complex IV inhibition in cerebellum. The authors propose that ketamine might be a useful therapy for major depression. |
Abstract
Rezin GT, Gonçalves CL, Daufenbach JF, Carvalho-Silva M, Borges LS, Vieira JS, Hermani FV, Comim CM, Quevedo J, Streck EL. Effect of chronic administration of ketamine on the mitochondrial respiratory chain activity caused by chronic mild stress. Recently, we reported that mitochondrial respiratory chain complexes I, III and IV were inhibited in the cerebral cortex and cerebellum of rats submitted to chronic mild stress (CMS) and that acute ketamine administration reversed this effect. Therefore, we investigated whether the inhibition of these enzymes may be reversed by chronic administration of ketamine. Adult male Wistar rats were submitted to CMS and chronically treated with ketamine. After 40 days of CMS, consumption of sweet food, adrenal gland weight, body weight and enzymatic activity of the complexes were measured. We verified that CMS decreased the intake of sweet food, increased the adrenal gland weight and the control group gained weight after 40 days but the stressed group did not; ketamine administration reversed these effects. We also verified that chronic administration of ketamine reversed the inhibition of complexes I, III and IV in cerebral cortex. However, in cerebellum, only complex IV inhibition was reversed. The chronic ketamine administration partially reverses the inhibition caused by CMS. We hypothesise that CMS inhibits complexes I, III and IV activities and that chronic administration of ketamine administration partially reverses such an effect. Therefore, it seems reasonable to propose that ketamine administration might be a useful therapy for patients affected by major depression.
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
Cites 3
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats. Revista Brasileira de Psiquiatria September 2009
- Acute administration of ketamine reverses the inhibition of mitochondrial respiratory chain induced by chronic mild stress. Brain Research Bulletin August 14, 2009