Unique Effects of (R)-Ketamine Compared to (S)-Ketamine on EEG Theta Power in Rats.
Dóra Pothorszki, Szabolcs Koncz, Dóra Török, Noémi Papp, György Bagdy
Pharmaceuticals February 1, 2024 DOI: 10.3390/ph17020194 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Wistar rats |
| Interventions | (R)-ketamine (S)-ketamine |
| Dose | 7.5, 15, 30 mg/kg i.p. for (R)-ketamine; 7.5 and 15 mg/kg i.p. for (S)-ketamine |
| Duration | 23 hours |
| Topics | Esketamine Ketamine Neuroplasticity |
| Keywords | Rem sleep Antidepressant Cognition Electroencephalography Memory Quantitative EEG Theta rhythm Psychopharmacology Brain Waves EEG Neural oscillations Ketamine esketamine Dissociative anesthetics |
| Citations | 7 |
| Key findings | (R)-ketamine dose-dependently increased EEG theta power during wakefulness and REM sleep for 23 hours, while (S)-ketamine did not. |
Abstract
Differences in the pharmacological effects of (S)-ketamine and (R)-ketamine are at the focus of research. Clinical data and our rat studies confirmed the antidepressant effect of (S)- but not (R)-ketamine, with similar differences in quantitative electroencephalogram (EEG) and sleep effects. In contrast, studies mainly on mice showed some stronger, preferable effects of (R)-ketamine. EEG theta (5-9 Hz) rhythm originates from the hippocampus, and its power is associated with cognitive functions, attention, and decreased anxiety. To find a brain parameter that is not associated with the antidepressant effect of drugs and may confirm potent in vivo effects of (R)-ketamine in rats, theta EEG power-inducing effects of the two enantiomers were measured and compared for 23 h. EEG-equipped Wistar rats were treated with (R)-ketamine (7.5, 15, 30 mg/kg i.p.), (S)-ketamine (7.5 and 15 mg/kg i.p.), or vehicle at the beginning of the passive phase. Frontoparietal EEG, electromyogram, and motor activity were recorded. (R)-ketamine but not (S)-ketamine dose-dependently increased EEG theta power during wakefulness and rapid eye movement (REM) sleep for 23 h. These results suggest that (R)-ketamine has an effect on a hippocampal function that was not affected by (S)-ketamine and may be associated with neural plasticity and memory encoding.
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
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. Biomedicines October 9, 2024
- (R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders. International Journal of Molecular Sciences June 20, 2024
- Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications. Frontiers in Pharmacology 2024
- Differential effects of ketamine enantiomers on EEG parameters including the gamma-delta shift phenomenon. British Journal of Pharmacology June 1, 2026
Cites 9
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability Molecular Psychiatry April 15, 2021
- The Antidepressant Actions of Ketamine and its Enantiomers Pharmacology & Therapeutics May 1, 2023
- (R)-Ketamine Induces a Greater Increase in Prefrontal 5-HT Release Than (S)-Ketamine and Ketamine Metabolites via an AMPA Receptor-Independent Mechanism The International Journal of Neuropsychopharmacology July 16, 2019
and 4 more in the library