ArticlePsychopharmacology2016
Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner.
Article in Psychopharmacology, 2016. 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, 41 citations in OpenAlex.
- Convergent neuroimmune signaling underlying rapid antidepressant response to ketamine and psychedelics.Molecular psychiatry · 2026Article
- The Olfactory Bulbectomy Model of Depression: Brief History, Current Status and Critique.Brain sciences · 2025Review
- Ketamine differentially affects implicit and explicit memory processes in rats.Psychopharmacology · 2025Article
- Understanding the Role of Oxidative Stress, Neuroinflammation and Abnormal Myelination in Excessive Aggression Associated with Depression: Recent Input from Mechanistic Studies.International journal of molecular sciences · 2023Review
- Low doses of ketamine and guanosine abrogate corticosterone-induced anxiety-related behavior, but not disturbances in the hippocampal NLRP3 inflammasome pathway.Psychopharmacology · 2021Article
- A Reliable High-Throughput Screening Model for Antidepressant.International journal of molecular sciences · 2021Article
- Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Review
- Guanosine fast onset antidepressant-like effects in the olfactory bulbectomy mice model.Scientific reports · 2020Article
- Ketamine induces immediate and delayed alterations of OCD-like behavior.Psychopharmacology · 2020Article
- Hippocampus Metabolic Disturbance and Autophagy Deficiency in Olfactory Bulbectomized Rats and the Modulatory Effect of Fluoxetine.International journal of molecular sciences · 2019Article
- Mechanisms of ketamine action as an antidepressant.Molecular psychiatry · 2018Review
- Convergent Mechanisms Underlying Rapid Antidepressant Action.CNS drugs · 2018Review
- Identifying fast-onset antidepressants using rodent models.Molecular psychiatry · 2017Review
- Revealing brain mechanisms of mTOR-mediated translational regulation: Implications for chronic pain.Neurobiology of pain (Cambridge, Mass.)Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe aim of our study was to test whether ketamine produces an antidepressant effect in animal model of olfactory bulbectomy and assess the role of mammalian target of rapamycin (mTOR) pathway in ketamine's antidepressant effect.
methodsBulbectomized (OBX) rats and sham controls were assigned to four subgroups according to the treatment they received (ketamine, saline, ketamine + rapamycin, and saline + rapamycin). The animals were subjected to open field (OF), elevated plus maze (EPM), passive avoidance (PA), Morris water maze (MWM), and Carousel maze (CM) tests. Blood samples were collected before and after drug administration for analysis of phosphorylated mTOR level. After behavioral testing, brains were removed for evaluation of brain-derived neurotrophic factor (BDNF) in prefrontal cortex (PFC) and hippocampus.
resultsKetamine normalized hyperactivity of OBX animals in EPM and increased the time spent in open arms. Rapamycin pretreatment resulted in elimination of ketamine effect in EPM test. In CM test, ketamine + rapamycin administration led to cognitive impairment not observed in saline-, ketamine-, or saline + rapamycin-treated OBX rats. Prefrontal BDNF content was significantly decreased, and level of mTOR was significantly elevated in OBX groups.
conclusionsOBX animals significantly differed from sham controls in most of the tests used. Treatment had more profound effect on OBX phenotype than controls. Pretreatment with rapamycin eliminated the anxiolytic and antidepressant effects of ketamine in task-dependent manner. The results indicate that ketamine + rapamycin application resulted in impaired stress responses manifested by cognitive deficits in active place avoidance (CM) test. Intensity of stressor (mild vs. severe) used in the behavioral tests had opposite effect on controls and on OBX animals.
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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.