ArticleFrontiers in psychiatry2020
The Antidepressant-Like Effects of a Clinically Relevant Dose of Ketamine Are Accompanied by Biphasic Alterations in Working Memory in the Wistar Kyoto Rat Model of Depression.
Article in Frontiers in psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- The Wistar-Kyoto rat as a model relevant to inattentive ADHD: substrain variability and affective comorbidity.Pharmacological reports : PR · 2026Review
- Hippocampal subfield differences in people with and without recreational ketamine use: Insights from multi-modal neuroimaging.Addiction (Abingdon, England) · 2026Article
- Divergent behavioral strategies in Wistar and Wistar-Kyoto rats in a naturalistic task reveal mood disorder phenotypes.iScience · 2026Article
- Drug-specific recovery of long-term memory and visual discrimination after anaesthetic-induced unconsciousness in rats.British journal of anaesthesia · 2025Article
- Bioactive ketamine metabolite exerts in vivo neuroplastogenic effects to improve hippocampal function in a treatment-resistant depression model.Cell reports · 2025Article
- Chronic Stress-Associated Depressive Disorders: The Impact of HPA Axis Dysregulation and Neuroinflammation on the Hippocampus-A Mini Review.International journal of molecular sciences · 2025Review
- GM-1020: a novel, orally bioavailable NMDA receptor antagonist with rapid and robust antidepressant-like effects at well-tolerated doses in rodents.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Rapid-acting antidepressant drugs modulate affective bias in rats.Science translational medicine · 2024Article
- Behavioral sensitization and tolerance induced by repeated treatment with ketamine enantiomers in male Wistar rats.PloS one · 2024Article
- The dynamic strategy shifting task: Optimisation of an operant task for assessing cognitive flexibility in rats.Frontiers in psychiatry · 2024Article
- Preclinical models of treatment-resistant depression: challenges and perspectives.Pharmacological reports : PR · 2023Review
- Traxoprodil Produces Antidepressant-Like Behaviors in Chronic Unpredictable Mild Stress Mice through BDNF/ERK/CREB and AKT/FOXO/Bim Signaling Pathway.Oxidative medicine and cellular longevity · 2023Article
- The Wistar Kyoto Rat: A Model of Depression Traits.Current neuropharmacology · 2023Article
- Mangiferin Alleviates Postpartum Depression-Like Behaviors by Inhibiting MAPK Signaling in Microglia.Frontiers in pharmacology · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Major depressive disorder (MDD) is the leading cause of disability worldwide. The majority of antidepressant drugs require several weeks or months of treatment to demonstrate efficacy and a subset of patients are resistant to such interventions. Ketamine demonstrates rapid and long-lasting antidepressant effects in treatment resistant patients; however, side effects may limit its widespread clinical utility. The pharmaceutical industry is engaged in developing novel rapid-acting antidepressant drugs and the establishment of clinically relevant assays are needed to advance this process. Wistar Kyoto (WKY) rats are a valuable model of many of the characteristics of MDD and their resistance to selective serotonin reuptake inhibitors (SSRIs) in several behavioral paradigms emulates treatment resistance in clinical populations. Here, we confirmed the depressive-like phenotype of WKY rats in comparison to Sprague Dawley rats, characterized by increased immobility in the forced swim test, decreased locomotor activity and entries to the centre in the open field test, anhedonia in the female urine sniffing test and working memory deficits in the delayed non-match to position task. Single subcutaneous administration of 5 mg/kg ketamine in WKY rats mirrored the plasma exposure produced by the antidepressant dose in the clinic and rescued depressive-like behaviors. The same dose induced transient side effects, including decreased locomotor activity and reduced positive affect-associated vocalizations. Furthermore, ketamine acutely impaired working memory but induced pro-cognitive effects at a later time point. These data confirm the WKY rat as a preclinical model of depression. Ketamine's efficacy in recovering this depressive-like phenotype while inducing transient dissociative-like effects supports this as a translational model suitable for investigating novel antidepressant drugs.
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