ReviewInternational journal of molecular sciences2021
The Role of Central Serotonin Neurons and 5-HT Heteroreceptor Complexes in the Pathophysiology of Depression: A Historical Perspective and Future Prospects.
Review in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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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
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Association of platelet-to-lymphocyte ratio with depression risk: a systematic review and meta-analysis.Frontiers in psychiatry · 2025Pooled it
- Jianpi Yiwei Granules for Chemotherapy-Induced Gastrointestinal Reactions: A Randomized Double-Blind Placebo-Controlled Trial.Anti-cancer agents in medicinal chemistry · 2026Trial
- Pharmacogenomics of Major Depressive Disorder in Indigenous Amazonian Populations.Clinical pharmacology and therapeutics · 2026Article
- Prebiotics attenuate depressive-like behavior, neuroinflammation and synaptic plasticity in Parkinson's disease by modulating butyrate-producing gut bacteria.Inflammopharmacology · 2026Article
- Dynamic changes in hemispheric lateralization in major depressive disorder correlate with neurotransmitter and genetic profiles: a DIRECT consortium study.Translational psychiatry · 2025Article
- Xiaoyaosan modulates gut-brain metabolic pathways and brain microstructure in depression: a multi-omics insight.Chinese medicine · 2025Article
- A novel insight into the femtosecond induced nonlinear response of monoamine neurotransmitters through experimental and in silico approaches.Scientific reports · 2025Article
- Association of HTR1F with Prognosis, Tumor Immune Microenvironment, and Drug Sensitivity in Cancer: A Multi-Omics Perspective.Biomedicines · 2025Article
- Review
- Diazepine Agonists of the 5-HTJournal of medicinal chemistry · 2025Article
- Clinical characteristics and short-term outcomes of migraine with patent foramen ovale: a comparative study.European journal of medical research · 2025Article
- Bidirectional relationships between physical exercise and depressive symptoms among Chinese older adults evidence from the China family panel studies.Scientific reports · 2025Article
- Alterations of circulating exosomal microRNAs in an LPS-induced depression model of male mice: Potential role in the anti-depressive effects of acupuncture.Physiological reports · 2025Article
- Research progress on melatonin, 5-HT, and orexin in sleep disorders of children with autism spectrum disorder.Biomolecules & biomedicine · 2025Review
- Pharmacodynamic, pharmacokinetic and rat brain receptor occupancy profile of NLX-112, a highly selective 5-HTNaunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Association of Hallucinogen Use With Psychosocial Outcomes: Secondary Analysis of the Spinal Cord Injury Model Systems Database.Topics in spinal cord injury rehabilitation · 2025Article
- Effects of microsurgery on short-term serum neurotransmitter levels and long-term cerebral neurological function in elderly patients with spontaneous intracerebral hemorrhage.Frontiers in neurology · 2025Article
- Repetitive transcranial magnetic stimulation elevates the serum levels of neurotrophic factors and serotonin and its metabolites in patients with ischemic stroke.Frontiers in neurology · 2025Article
- Oleanolic Acid Cubic Liquid Crystal Nanoparticle-Based Thermosensitive Gel Attenuates Depression Symptoms in Chronic Unpredictable Mild Stress Rats.Drug design, development and therapy · 2025Article
- The Role of Estrogen across Multiple Disease Mechanisms.Current issues in molecular biology · 2024Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 6 countries.
Funding
Abstract
Serotonin communication operates mainly in the extracellular space and cerebrospinal fluid (CSF), using volume transmission with serotonin moving from source to target cells (neurons and astroglia) via energy gradients, leading to the diffusion and convection (flow) of serotonin. One emerging concept in depression is that disturbances in the integrative allosteric receptor-receptor interactions in highly vulnerable 5-HT1A heteroreceptor complexes can contribute to causing major depression and become novel targets for the treatment of major depression (MD) and anxiety. For instance, a disruption and/or dysfunction in the 5-HT1A-FGFR1 heteroreceptor complexes in the raphe-hippocampal serotonin neuron systems can contribute to the development of MD. It leads inter alia to reduced neuroplasticity and potential atrophy in the raphe-cortical and raphe-striatal 5-HT pathways and in all its forebrain networks. Reduced 5-HT1A auto-receptor function, increased plasticity and trophic activity in the midbrain raphe 5-HT neurons can develop via agonist activation of allosteric receptor-receptor interactions in the 5-HT1A-FGFR1 heterocomplex. Additionally, the inhibitory allosteric receptor-receptor interactions in the 5-HT1AR-5-HT2AR isoreceptor complex therefore likely have a significant role in modulating mood, involving a reduction of postjunctional 5-HT1AR protomer signaling in the forebrain upon activation of the 5-HT2AR protomer. In addition, oxytocin receptors (OXTRs) play a significant and impressive role in modulating social and cognitive related behaviors like bonding and attachment, reward and motivation. Pathological blunting of the OXTR protomers in 5-HT2AR and especially in 5-HT2CR heteroreceptor complexes can contribute to the development of depression and other types of psychiatric diseases involving disturbances in social behaviors. The 5-HTR heterocomplexes are novel targets for the treatment of MD.
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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.