ArticleThe international journal of neuropsychopharmacology2018
Role of 5-HT1A Receptor Stimulation in the Medial Prefrontal Cortex in the Sustained Antidepressant Effects of Ketamine.
Article in The international journal of neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 86 citations in OpenAlex.
- The behavioural effects of the serotonin 1A receptor agonist buspirone on reward processing in healthy volunteers: A randomised, placebo-controlled study.Journal of psychopharmacology (Oxford, England) · 2026Trial
- Serotonergic and glutamatergic mechanisms converge in ketamine's rapid responses.Trends in neurosciences · 2026Review
- Progress in the Application of Esketamine During the Perioperative Period.Drug design, development and therapy · 2026Review
- Inhibition of SERT and NMDAR synergistically confers rapid antidepressant effects of ketamine.National science review · 2025Article
- [Translational psychiatry · 2025Article
- Ketamine in clinical practice: transitioning from anesthetic agent to psychiatric therapeutic.CNS spectrums · 2025Review
- Neuropharmacology of Ketamine and Its Use in the Treatment of Major Depressive Disorder: A Review.Cureus · 2025Review
- Targeting serotonin receptors with phytochemicals - an in-silico study.Scientific reports · 2024Article
- Genetic ablation of the isoform γ of PI3K decreases antidepressant efficacy of ketamine in male mice.IBRO neuroscience reports · 2024Article
- The 5-HTPsychopharmacology · 2023Article
- Article
- mGlu2/3 receptor antagonists for depression: overview of underlying mechanisms and clinical development.European archives of psychiatry and clinical neuroscience · 2023Review
- The Serotonin 1A (5-HTCNS drugs · 2023Review
- Role of the mesolimbic dopamine pathway in the antidepressant effects of ketamine.Neuropharmacology · 2023Review
- Single subanesthetic dose of ketamine produces delayed impact on brain [Frontiers in neuroscience · 2023Article
- Inhibition of FKBP51 induces stress resilience and alters hippocampal neurogenesis.Molecular psychiatry · 2022Article
- Review
- New monoamine antidepressant, hypidone hydrochloride (YL-0919), enhances the excitability of medial prefrontal cortex in mice via a neural disinhibition mechanism.Acta pharmacologica Sinica · 2022Article
- Molecular Signaling Mechanisms for the Antidepressant Effects of NLX-101, a Selective Cortical 5-HTPharmaceuticals (Basel, Switzerland) · 2022Article
- Novel Pharmacological Approaches to the Treatment of Depression.Life (Basel, Switzerland) · 2022Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: We previously reported that serotonergic transmission plays an important role in antidepressant effects of ketamine. However, detailed mechanisms have not been elucidated. Among the serotonin receptor subtypes, the serotonin1A receptor in the medial prefrontal cortex has an important role in depression. Here, we investigated the role of the medial prefrontal cortex serotonin1A receptor and its signaling mechanism in the antidepressant effects of ketamine. Methods: The role of serotonin1A receptor-mediated signaling mechanism (phosphoinositide-3 kinase/Akt) in the medial prefrontal cortex was examined in the mouse forced swimming test and western blotting. Results: Ketamine exerted antidepressant effects that lasted for 24 hours, and the sustained antidepressant effects were attenuated by intra-medial prefrontal cortex injection of a serotonin1A receptor antagonist, WAY100635. The sustained antidepressant effects were mimicked by intra- medial prefrontal cortex, but not systemic, administration of a serotonin1A receptor agonist, (±)-8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT). The sustained antidepressant effects of ketamine and 8-OH-DPAT were abrogated by intra- medial prefrontal cortex injection of a phosphoinositide-3 kinase inhibitor. Ketamine increased the phosphorylation of Akt in the medial prefrontal cortex at 60 minutes after administration, which was blocked by a serotonin1A receptor antagonist and a phosphoinositide-3 kinase inhibitor. Furthermore, the sustained antidepressant effects of ketamine and 8-OH-DPAT were attenuated by pretreatment of intra-medial prefrontal cortex injection of a mechanistic target of rapamycin complex-1 inhibitor. Conclusions: These results indicate that selective stimulation of the medial prefrontal cortex serotonin1A receptor and subsequent activation of the phosphoinositide-3 kinase/Akt/mechanistic target of rapamycin complex-1 pathway may be necessary for ketamine to exert the sustained antidepressant effects, and that this mechanism could be targeted to develop a novel and effective approach for treating depression.
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