ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Rapid anxiolytic effects of a 5-HT₄ receptor agonist are mediated by a neurogenesis-independent mechanism.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 161 citations in OpenAlex.
- Pro-cognitive effects of 5-HT4 receptor agonism in individuals with remitted depression.Psychological medicine · 2026Trial
- 5-HT4 Receptor Ligand RS67333 Modulates Striatal Acetylcholine and Dopamine Release via the Inhibition of Acetylcholinesterase.ACS chemical neuroscience · 2026Article
- Dup15q model mice exhibit impaired gastrointestinal motility and a constipation-like phenotype, alleviated by prucalopride.Translational psychiatry · 2026Article
- Early effects of a novel 5-HTThe British journal of psychiatry : the journal of mental science · 2026Article
- Prucalopride, a serotonin type 4 receptor agonist, induces fast anxiolytic/antidepressant effects and concomitant changes in the gut microbiota.NPJ biofilms and microbiomes · 2026Article
- The Complex Role of Serotonin-Dopamine-Glutamate Receptors in Major Depression.Advances in experimental medicine and biology · 2026Review
- Sex-dependent serotonergic signaling across development: molecular mechanisms shaping vulnerability to neurodevelopmental and mental disorders.Frontiers in pharmacology · 2026Review
- Impact of 5-HT4 Receptors on Neuron-Glial Network Activity In Vitro.International journal of molecular sciences · 2025Article
- Combinatorial targeting of NMDARs and 5-HTAlzheimer's research & therapy · 2025Article
- Chronic, combinatorial targeting of NMDARs and 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Psychiatric Adverse Effects From Prucalopride in a Medically Complex Adolescent.Case reports in pediatrics · 2025Article
- Neurobiological and therapeutic landmarks of depression associated with Alzheimer's disease dementia.Frontiers in aging neuroscience · 2025Review
- Sex hormones and serotonin 4 receptor brain binding in men with and without major depressive disorder.Neuroscience applied · 2025Article
- Ketamine metabolism via hepatic CYP450 isoforms contributes to its sustained antidepressant actions.Neuropharmacology · 2024Article
- Association between a selective 5-HTThe British journal of psychiatry : the journal of mental science · 2024Article
- Pharmacological inhibition of Kir4.1 evokes rapid-onset antidepressant responses.Nature chemical biology · 2024Article
- The Serotonin 4 Receptor Subtype: A Target of Particular Interest, Especially for Brain Disorders.International journal of molecular sciences · 2024Review
- Seizure-induced LIN28A disrupts pattern separation via aberrant hippocampal neurogenesis.JCI insight · 2024Article
- 5-HT4 receptor agonists treatment reduces tau pathology and behavioral deficit in the PS19 mouse model of tauopathy.Frontiers in cellular neuroscience · 2024Article
- Functional Dimerization of Serotonin Receptors: Role in Health and Depressive Disorders.International journal of molecular sciences · 2023Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Selective serotonin reuptake inhibitors (SSRIs) display a delayed onset of action of several weeks. Past work in naive rats showed that 5-HT₄ receptor agonists had rapid effects on depression-related behaviors and on hippocampal neurogenesis. We decided to investigate whether 5-HT₄ receptor stimulation was necessary for the effects of SSRIs in a mouse model of anxiety/depression, and whether hippocampal neurogenesis contributed to these effects. Using the mouse corticosterone model of anxiety/depression, we assessed whether chronic treatment with a 5-HT₄ receptor agonist (RS67333, 1.5 mg/kg/day) had effects on anxiety- and depression-related behaviors, as well as on hippocampal neurogenesis in comparison with chronic fluoxetine treatment (18 mg/kg/day). Then, using our anxiety/depression model combined with ablation of hippocampal neurogenesis, we investigated whether neurogenesis was necessary for the behavioral effects of subchronic (7 days) or chronic (28 days) RS67333 treatment. We also assessed whether a 5-HT₄ receptor antagonist (GR125487, 1 mg/kg/day) could prevent the behavioral and neurogenic effects of fluoxetine. Chronic treatment with RS67333, similar to fluoxetine, induced anxiolytic/antidepressant-like activity and stimulated adult hippocampal neurogenesis, specifically facilitating maturation of newborn neurons. However, unlike fluoxetine, anxiolytic effects of RS67333 were already present after 7 days and did not require hippocampal neurogenesis. Chronic treatment with GR125487 prevented both anxiolytic/antidepressant-like and neurogenic effects of fluoxetine, indicating that 5-HT₄ receptor activation is necessary for these effects of SSRIs. 5-HT₄ receptor stimulation could represent an innovative and rapid onset therapeutic approach to treat depression with comorbid anxiety.
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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.