ArticlePsychopharmacology2016
Comparison of R-ketamine and rapastinel antidepressant effects in the social defeat stress 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 50 papers.
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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.
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Who cites it
50 citing papers in PubMed, 93 citations in OpenAlex.
- Chronic unpredictable mild Stress- induced neurobehavioral and metabolic alteration: insights into molecular mechanisms and emerging therapeutic Strategies".Psychopharmacology · 2026Review
- AI-driven decoding of naturalistic behaviors enables tailored detection of depressive-like behavior in mice.Nature communications · 2025Article
- Unraveling the brain expression of bdnf in a mouse model of anorexia nervosa.Translational psychiatry · 2025Article
- AMPA receptor diffusional trapping machinery as an early therapeutic target in neurodegenerative and neuropsychiatric disorders.Translational neurodegeneration · 2025Review
- New Insights into Contradictory Changes in Brain-Derived Neurotrophic Factor (BDNF) in Rodent Models of Posttraumatic Stress Disorder (PTSD).Neurochemical research · 2024Review
- Major depressive disorder: hypothesis, mechanism, prevention and treatment.Signal transduction and targeted therapy · 2024Review
- Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Changes in social, sexual, and hedonic behaviors in rats in response to stress and restoration by a negative allosteric modulator of α5-subunit containing GABA receptor.Behavioural brain research · 2023Article
- Article
- Changes in synaptic markers after administration of ketamine or psychedelics: a systematic scoping review.Frontiers in psychiatry · 2023Article
- Zelquistinel Is an Orally Bioavailable Novel NMDA Receptor Allosteric Modulator That Exhibits Rapid and Sustained Antidepressant-Like Effects.The international journal of neuropsychopharmacology · 2022Article
- Downregulation of surface AMPA receptor expression in the striatum following prolonged social isolation, a role of mGlu5 receptors.IBRO neuroscience reports · 2022Article
- Review
- A Role of BDNF in the Depression Pathogenesis and a Potential Target as Antidepressant: The Modulator of Stress Sensitivity "Shati/Nat8l-BDNF System" in the Dorsal Striatum.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Striatal Shati/Nat8l-BDNF pathways determine the sensitivity to social defeat stress in mice through epigenetic regulation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Metaplastic Effects of Ketamine and MK-801 on Glutamate Receptors Expression in Rat Medial Prefrontal Cortex and Hippocampus.Molecular neurobiology · 2021Article
- Role of BDNF in the pathophysiology and treatment of depression: Activity-dependent effects distinguish rapid-acting antidepressants.The European journal of neuroscience · 2021Review
- Novel Insights Into the Neurobiology of the Antidepressant Response From Ketamine Research: A Mini Review.Frontiers in behavioral neuroscience · 2021Review
- Methionine mediates resilience to chronic social defeat stress by epigenetic regulation of NMDA receptor subunit expression.Psychopharmacology · 2020Article
- Bidirectional Dysregulation of AMPA Receptor-Mediated Synaptic Transmission and Plasticity in Brain Disorders.Frontiers in synaptic neuroscience · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleThe N-methyl-D-aspartate (NMDA) receptor antagonists, including R-ketamine and rapastinel (formerly GLYX-13), show rapid antidepressant effects in animal models of depression.
objectiveWe compared the rapid and sustained antidepressant effects of R-ketamine and rapastinel in the social defeat stress model.
resultsIn the tail suspension and forced swimming tests, R-ketamine (10 mg/kg, intraperitoneal (i.p.)) or rapastinel (10 mg/kg, i.p.) significantly attenuated the increased immobility time in the susceptible mice, compared with the vehicle-treated group. In the sucrose preference test, both compounds significantly enhanced the reduced preference in susceptible mice 2, 4, or 7 days after a single injection. All mice were sacrificed 8 days after a single injection. Western blot analyses showed that R-ketamine, but not rapastinel, significantly attenuated the reduced brain-derived neurotrophic factor (BDNF)-TrkB signaling, postsynaptic density protein 95 (PSD-95), and GluA1 (a subtype of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor) in the prefrontal cortex, dentate gyrus, and CA3 of the hippocampus in the susceptible mice. In contrast, both compounds had no effect against the increased BDNF-TrkB signaling, PSD-95, and GluA1 seen in the nucleus accumbens of susceptible mice. Moreover, sustained antidepressant effect of R-ketamine (3 mg/kg, intravenous (i.v.)), but not rapastinel (3 mg/kg, i.v.), was detected 7 days after a single dose.
conclusionsThese results highlight R-ketamine as a longer lasting antidepressant compared with rapastinel in social defeat stress model. It is likely that synaptogenesis including BDNF-TrkB signaling in the prefrontal cortex (PFC) and hippocampus may be required for the mechanisms promoting this sustained antidepressant effect.
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Registered trials
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.