ArticleThe international journal of neuropsychopharmacology2023
(S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats.
Article in The international journal of neuropsychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07610343 (Impact of Intranasal Dexmedetomidine-esketamine on Sleep Quality and Cognitive Function in Older Adults With Mild-to-moderate Cognitive Impairment), which is not on this map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Impact of Intranasal Dexmedetomidine-esketamine on Sleep Quality and Cognitive Function in Older Adults With Mild-to-moderate Cognitive Impairment: a Randomized, Double-blind, and Placebo-controlled Trial
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Efficacy and safety of esketamine on major depression, postpartum depression and perioperative depression: a systematic review and meta-analysis.Molecular psychiatry · 2026Pooled it
- The Effect of Intraoperative Infusion of Different Doses of Esketamine on the Quality of Recovery in Elderly Patients Undergoing Knee Arthroplasty.Drug design, development and therapy · 2026Trial
- Esketamine Optimized the Efficacy of Dexmedetomidine in Treating Sleep Disorders with Comorbid Depression.Neuropsychiatric disease and treatment · 2025Trial
- Pleiotropic modulation of the gut-brain-lung axis by ketamine and its enantiomers.Molecular psychiatry · 2026Review
- Restorative or Disruptive? Effects of Antidepressants on Sleep Architecture in Depression.CNS drugs · 2026Review
- Increase of the AMPA-evoked response of pyramidal neurons in the rat medial prefrontal cortex following acute administration of ketamine and S-ketamine, but not R-ketamine.The international journal of neuropsychopharmacology · 2026Article
- Insomnia and Esketamine Add-On Therapy to Antidepressant Therapy in Patients with Treatment-Resistant Depression-A Pilot Study.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Effects of the subanesthetic dose of esketamine on postoperative sleep quality in patients undergoing modified radical mastectomy: a randomized, double-blind controlled trial.Frontiers in medicine · 2025Article
- Clinical Benefits and Challenges of Esketamine in Elderly Patients During the Perioperative Period.Drug design, development and therapy · 2025Review
- Ketamine Reduces Avoidance Responses During Re-Exposition to Aversive Stimulus: Comparison Between (Brain sciences · 2024Article
- Neuroplasticity and Mechanisms of Action of Acute and Chronic Treatment with Antidepressants in Preclinical Studies.Biomedicines · 2024Review
- (International journal of molecular sciences · 2024Review
- Article
- Unique Effects of (R)-Ketamine Compared to (S)-Ketamine on EEG Theta Power in Rats.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Behavioral sensitization and tolerance induced by repeated treatment with ketamine enantiomers in male Wistar rats.PloS one · 2024Article
- Esketamine Inhibits Cocaine-Seeking Behaviour Subsequent to Various Abstinence Conditions in Rats.Biomolecules · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRacemic ketamine consists of two enantiomers, namely (R)-ketamine and (S)-ketamine, with distinguishable pharmacological properties. Both enantiomers have been reported to show rapid antidepressant effects in rodents. Currently, the (S)-enantiomer has been approved for the treatment of major depression, whereas (R)-ketamine failed to show antidepressant effect in recent clinical studies. Major depressive disorder is frequently characterized by disinhibition of rapid eye movement (REM) sleep and disruption of non-REM (NREM) sleep. Racemic ketamine and most conventional antidepressants affect these parameters. However, it remains largely unknown which enantiomer is responsible for these effects.
methodsHere, we compared acute effects of the two ketamine enantiomers (15 mg/kg i.p.) on different sleep-wake stages in freely moving, EEG-equipped rats. We also evaluated the antidepressant-like activity of the enantiomers in a chronic restraint stress model of depression.
results(S)-ketamine but not (R)-ketamine increased REM sleep latency and decreased REM sleep time at 2 and 3 hours, and increased electroencephalogram delta power during NREM sleep. In addition, only (S)-ketamine increased wakefulness and decreased NREM sleep in the first 2 hours. In the forced swimming test, only (S)-ketamine decreased the immobility time of chronically stressed rats.
conclusionEffects of the two ketamine enantiomers on rat sleep-wake architecture and behavior are markedly different when administered in the same dose. (S)-ketamine remarkably affects the sleep-wake cycle and very likely sleep-related neuroplasticity, which may be relevant for its antidepressant efficacy. Our results regarding (R)-ketamine's lack of effect on vigilance and behavior are in line with recent clinical studies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.