ReviewFrontiers in behavioral neuroscience2015
Chronic SSRI stimulation of astrocytic 5-HT2B receptors change multiple gene expressions/editings and metabolism of glutamate, glucose and glycogen: a potential paradigm shift.
Review in Frontiers in behavioral neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- The Association Between Antidepressant Effect of SSRIs and Astrocytes: Conceptual Overview and Meta-analysis of the Literature.Neurochemical research · 2021Pooled it
- Review
- The Serotonin 2B (5-HT2B) Receptor: A Narrative Review of Preclinical and Clinical Evidence on the Safety Considerations and Therapeutic Potential for the Treatment of Depression.Clinical pharmacology and therapeutics · 2026Review
- Beyond neurotransmission: the roles of serotonylation in physiological and pathological processes.Cellular & molecular biology letters · 2026Review
- Metabolic interactions in the brain: the crucial roles of neurons, astrocytes, and microglia in health and disease.Frontiers in neuroscience · 2026Review
- Disrupted NAD(P) Metabolism and Xanthine Dehydrogenase in a Stress-Induced Rat Model of Depression: NMR Metabolomics Insights.Metabolites · 2024Article
- Cytokines and Madness: A Unifying Hypothesis of Schizophrenia Involving Interleukin-22.International journal of molecular sciences · 2024Review
- [Coenzyme Q10 alleviates depression-like behaviors in mice with chronic restraint stress by down-regulating the pyroptosis signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Astrocytes in human central nervous system diseases: a frontier for new therapies.Signal transduction and targeted therapy · 2023Review
- Disruption of the Mammalian Ccr4-Not Complex Contributes to Transcription-Mediated Genome Instability.Cells · 2023Article
- Electroacupuncture prevents astrocyte atrophy to alleviate depression.Cell death & disease · 2023Article
- Article
- Astrocytes in Post-traumatic Stress Disorder.Neuroscience bulletin · 2022Review
- Characterizing cerebral metabolite profiles in anorexia and bulimia nervosa and their associations with habitual behavior.Translational psychiatry · 2022Article
- Ketamine Alters Functional Plasticity of Astroglia: An Implication for Antidepressant Effect.Life (Basel, Switzerland) · 2021Review
- Modulation of the Serotonergic Receptosome in the Treatment of Anxiety and Depression: A Narrative Review of the Experimental Evidence.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Astrocyte Bioenergetics and Major Psychiatric Disorders.Advances in neurobiology · 2021Review
- Astroglial Serotonin Receptors as the Central Target of Classic Antidepressants.Advances in neurobiology · 2021Article
- Ketamine Action on Astrocytes Provides New Insights into Rapid Antidepressant Mechanisms.Advances in neurobiology · 2021Review
- Pharmacological stimulation of sigma-1 receptor promotes activation of astrocyte via ERK1/2 and GSK3β signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is firmly believed that the mechanism of action of SSRIs in major depression is to inhibit the serotonin transporter, SERT, and increase extracellular concentration of serotonin. However, this undisputed observation does not prove that SERT inhibition is the mechanism, let alone the only mechanism, by which SSRI's exert their therapeutic effects. It has recently been demonstrated that 5-HT2B receptor stimulation is needed for the antidepressant effect of fluoxetine in vivo. The ability of all five currently used SSRIs to stimulate the 5-HT2B receptor equipotentially in cultured astrocytes has been known for several years, and increasing evidence has shown the importance of astrocytes and astrocyte-neuronal interactions for neuroplasticity and complex brain activity. This paper reviews acute and chronic effects of 5-HT2B receptor stimulation in cultured astrocytes and in astrocytes freshly isolated from brains of mice treated with fluoxetine for 14 days together with effects of anti-depressant therapy on turnover of glutamate and GABA and metabolism of glucose and glycogen. It is suggested that these events are causally related to the mechanism of action of SSRIs and of interest for development of newer antidepressant drugs.
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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.