ArticlePsychopharmacology2016
Differential interaction with the serotonin system by S-ketamine, vortioxetine, and fluoxetine in a genetic rat model of depression.
Article in Psychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.
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Who cites it
40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Use of vortioxetine in different neurological fields: a systematic review and future perspectives.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Pooled it
- Efficacy and safety of esketamine for pediatric gastrointestinal endoscopy: a meta-analysis and trial sequential analysis.Frontiers in pharmacology · 2024Pooled it
- Vortioxetine for depression in adults.The Cochrane database of systematic reviews · 2017Pooled it
- Translating the immediate effects of S-Ketamine using hippocampal subfield analysis in healthy subjects-results of a randomized controlled trial.Translational psychiatry · 2021Trial
- Investigation of Potential Therapeutic Effects of New Rapid-Acting Antidepressant Drugs (RAADs) Using Stress-Based Models of Depression.Biomolecules · 2026Review
- Akkermansia Muciniphila vs. Fluoxetine: Amelioration of Depression-like Behaviors and Cognitive Dysfunction Through Distinct Neurobiological Mechanisms.Probiotics and antimicrobial proteins · 2026Article
- Multidimensional Data-Driven Mechanistic Insights into Anle Tablets for Depression Treatment through Molecular Docking and Dynamics.Current pharmaceutical design · 2026Article
- Vortioxetine effectiveness in the treated major depressive disorder patients in Saudi Arabia.Annals of general psychiatry · 2025Article
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers.Journal of anesthesia and translational medicine · 2025Review
- Depression-like effects induced by chronic unpredictable mild stress in mice are rapidly reversed by a partial negative allosteric modulator of mGluPsychopharmacology · 2025Article
- Voritoxetine induced generalised pruritus: A preventable incident.Indian journal of psychiatry · 2025Article
- An Updated Bio-Behavioral Profile of the Flinders Sensitive Line Rat: Reviewing the Findings of the Past Decade.Pharmacology research & perspectives · 2025Review
- Ultrasonic vocalisations in the Flinders Sensitive Line rat, a genetic animal model of depression.Acta neuropsychiatrica · 2025Article
- HumanFrontiers in neuroscience · 2025Article
- Partial mGluPharmacological reports : PR · 2024Article
- (S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats.The international journal of neuropsychopharmacology · 2023Article
- The pathophysiology of rhabdomyolysis in ungulates and rats: towards the development of a rodent model of capture myopathy.Veterinary research communications · 2023Review
- Catecholaminergic and Cholinergic Systems Mediate Beneficial Effect of Vortioxetine on Diabetes-Induced Neuropathic Pain.Biomedicines · 2023Article
- Post-Partum Depression Lactating Rat Model for Evaluating Ketamine's Safety as a Pharmacotherapeutic Treatment: Roles in Cardiac and Urinary Function.Journal of cardiovascular development and disease · 2022Article
- The role of serotonin neurotransmission in rapid antidepressant actions.Psychopharmacology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleThe mechanisms mediating ketamine's antidepressant effect have only been partly resolved. Recent preclinical reports implicate serotonin (5-hydroxytryptamine; 5-HT) in the antidepressant-like action of ketamine. Vortioxetine is a multimodal-acting antidepressant that is hypothesized to exert its therapeutic activity through 5-HT reuptake inhibition and modulation of several 5-HT receptors.
objectivesThe objective of this study was to evaluate the therapeutic-like profiles of S-ketamine, vortioxetine, and the serotonin reuptake inhibitor fluoxetine in response to manipulation of 5-HT tone.
methodFlinders Sensitive Line (FSL) rats, a genetic model of depression, were depleted of 5-HT by repeated administration of 4-chloro-DL-phenylalanine methyl ester HCl (pCPA). Using pCPA-pretreated and control FSL rats, we investigated the acute and sustained effects of S-ketamine (15 mg/kg), fluoxetine (10 mg/kg), or vortioxetine (10 mg/kg) on recognition memory and depression-like behavior in the object recognition task (ORT) and forced swim test (FST), respectively.
resultsThe behavioral phenotype of FSL rats was unaffected by 5-HT depletion. Vortioxetine, but not fluoxetine or S-ketamine, acutely ameliorated the memory deficits of FSL rats in the ORT irrespective of 5-HT tone. No sustained effects were observed in the ORT. In the FST, all three drugs demonstrated acute antidepressant-like activity but only S-ketamine had sustained effects. Unlike vortioxetine, the antidepressant-like responses of fluoxetine and S-ketamine were abolished by 5-HT depletion.
conclusionsThese observations suggest that the acute and sustained antidepressant-like effects of S-ketamine depend on endogenous stimulation of 5-HT receptors. In contrast, the acute therapeutic-like effects of vortioxetine on memory and depression-like behavior may be mediated by direct activity at 5-HT receptors.
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