Downregulation in the human and mice cerebella after ketamine versus ketamine plus ethanol treatment.
W M Chan, Jie Xu, Ming Fan, Yanling Jiang, Therese Y M Tsui, Maria S M Wai, W P Lam, D T Yew
Microscopy research and technique March 2012 DOI: 10.1002/jemt.21052 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case study with animal experiment Case report Peer reviewed |
|---|---|
| Sample size | 3 |
| Population | Habitual ketamine users (n = 3) and male ICR mice |
| Interventions | Ketamine Ethanol |
| Dose | 30 mg/kg intraperitoneally (ketamine); 0.5 mL 12% orally (ethanol, mice); 12%, 200 mL (alcohol, human participants) |
| Duration | 3 months (mouse treatment); 1 h before fMRI test (alcohol consumption in humans) |
| Measures | functional magnetic resonance imaging (fMRI), silver staining, TUNEL test, two-way ANOVA |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine was associated with cerebellar damage: fewer Purkinje cells and more apoptotic cells in the cerebella of mice treated for three months, with apoptosis significantly greater in mice given both ketamine and ethanol (P < 0.001) than in controls. In three habitual ketamine users, cerebellum activation during limb movement decreased after alcohol consumption. The authors propose an interactive mechanism between ethanol and ketamine acting on the cerebellum. |
Abstract
To study the deleterious effects of ketamine and the potential interaction effects between ethanol and ketamine on the cerebellum, functional magnetic resonance imaging (fMRI) tests were performed on the habitual ketamine users (n = 3) when they flexed and extended their upper limbs. Another fMRI test was performed on the same participants in which they consumed alcohol (12%, 200 mL) 1 h before the test. Downregulation on the activity of cerebellum was observed and the level of activation in the cerebellum decreased dramatically in habitual ketamine users with alcohol consumption before the test. Further studies were performed by using male ICR mice receiving treatment of ketamine only [30 mg kg(-1) intraperitoneally (i.p.)] or ethanol only everyday (0.5 mL 12% orally) and those with coadministration of the above dosages of ketamine and ethanol for 3 months. Fewer Purkinje cells were observed in the cerebellar sections of ketamine treated mice under silver staining. For TUNEL test, a significant increase in the apoptotic cells were observed in the cerebella of the ketamine treated mice (P = 0.016) and of those with co-administration of ketamine and ethanol (P < 0.001), when compared with the control. A statistical significance (P < 0.001) in two-way ANOVA test indicated that there might be an interactive mechanism between ethanol and ketamine acting on the cerebellum.
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 4
- Brain damages in ketamine addicts as revealed by magnetic resonance imaging Frontiers in Neuroanatomy May 22, 2014
- Brain Changes Associated With Long-Term Ketamine Abuse, A Systematic Review Frontiers in Neuroanatomy March 18, 2022
- The effects of sub-anesthetic ketamine plus ethanol on behaviors and apoptosis in the prefrontal cortex and hippocampus of adolescent rats. Pharmacology, Biochemistry, and Behavior July 23, 2019
- The interactive effects of ketamine and ethanol on dopamine expression in the ventral tegmental area of rats. Neuropsychiatric Disease and Treatment 2018
Cites 6
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Study of a New Schizophrenomimetic Drug—Sernyl Archives of Neurology And Psychiatry March 1, 1959
- Mechanisms underlying ketamine-induced synaptic depression in rat hippocampus-medial prefrontal cortex pathway. Neuroscience March 17, 2011
- Reduced dorsal prefrontal gray matter after chronic ketamine use. Biological Psychiatry January 1, 2011
- Ethanol-like effects of thiopental and ketamine in healthy humans Journal of Psychopharmacology February 1, 2010
and 1 more in the library