ArticleMolecular psychiatry2014
Serotonin 2C receptor antagonists induce fast-onset antidepressant effects.
Article in Molecular psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
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- Characterisation of a touchscreen-based task for assessing cognitive judgement bias in mice: a new translational tool for affective state disorder drug screening.Psychopharmacology · 2026Article
- The Complex Role of Serotonin-Dopamine-Glutamate Receptors in Major Depression.Advances in experimental medicine and biology · 2026Review
- Somatostatin: Linking Cognition and Alzheimer Disease to Therapeutic Targeting.Pharmacological reviews · 2024Review
- Major depressive disorder: hypothesis, mechanism, prevention and treatment.Signal transduction and targeted therapy · 2024Review
- Subcortical serotonin 5HTNature communications · 2023Article
- Plasticity of synapses and reward circuit function in the genesis and treatment of depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- Chronic Trazodone and Citalopram Treatments Increase Trophic Factor and Circadian Rhythm Gene Expression in Rat Brain Regions Relevant for Antidepressant Efficacy.International journal of molecular sciences · 2022Article
- COVID-19 and olfactory dysfunction: a looming wave of dementia?Journal of neurophysiology · 2022Review
- Disruption of 5-hydroxytryptamine 1A receptor and orexin receptor 1 heterodimer formation affects novel G protein-dependent signaling pathways and has antidepressant effects in vivo.Translational psychiatry · 2022Article
- Decursinol-mediated antinociception and anti-allodynia in acute and neuropathic pain models in male mice: Tolerance and receptor profiling.Frontiers in pharmacology · 2022Article
- Evidence of an antidepressant-like effect of xylopic acid mediated by serotonergic mechanisms.Psychopharmacology · 2021Article
- GW117: A novel serotonin (5-HTCNS neuroscience & therapeutics · 2021Article
- EEG and Sleep Effects of Tramadol Suggest Potential Antidepressant Effects with Different Mechanisms of Action.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Uncovering the Underlying Mechanisms of Ketamine as a Novel Antidepressant.Frontiers in pharmacology · 2021Review
- Zebrafish as a Useful Tool in the Research of Natural Products With Potential Anxiolytic Effects.Frontiers in behavioral neuroscience · 2021Review
- Astroglial Serotonin Receptors as the Central Target of Classic Antidepressants.Advances in neurobiology · 2021Article
- Article
- 5-HT2C receptor blockade reverses SSRI-associated basal ganglia dysfunction and potentiates therapeutic efficacy.Molecular psychiatry · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Current antidepressants must be administered for several weeks to produce therapeutic effects. We show that selective serotonin 2C (5-HT2C) antagonists exert antidepressant actions with a faster-onset (5 days) than that of current antidepressants (14 days) in mice. Subchronic (5 days) treatment with 5-HT2C antagonists induced antidepressant behavioral effects in the chronic forced swim test (cFST), chronic mild stress (CMS) paradigm and olfactory bulbectomy paradigm. This treatment regimen also induced classical markers of antidepressant action: activation of cAMP response element-binding protein (CREB) and induction of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC). None of these effects were induced by subchronic treatment with citalopram, a prototypical selective serotonin reuptake inhibitor (SSRI). Local infusion of 5-HT2C antagonists into the ventral tegmental area was sufficient to induce BDNF in the mPFC, and dopamine D1 receptor antagonist treatment blocked the antidepressant behavioral effects of 5-HT2C antagonists. 5-HT2C antagonists also activated mammalian target of rapamycin (mTOR) and eukaryotic elongation factor 2 (eEF2) in the mPFC, effects recently linked to rapid antidepressant action. Furthermore, 5-HT2C antagonists reversed CMS-induced atrophy of mPFC pyramidal neurons. Subchronic SSRI treatment, which does not induce antidepressant behavioral effects, also activated mTOR and eEF2 and reversed CMS-induced neuronal atrophy, indicating that these effects are not sufficient for antidepressant onset. Our findings reveal that 5-HT2C antagonists are putative fast-onset antidepressants, which act through enhancement of mesocortical dopaminergic signaling.
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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.