ArticleCellular signalling2012
Functional significance of glycogen synthase kinase-3 regulation by serotonin.
Article in Cellular signalling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 64 citations in OpenAlex.
- Investigating whether alcohol is transformed to norepinephrine or dopamine in the mouse brain.Pharmacological reports : PR · 2025Article
- Sertraline as a Multi-Target Modulator of AChE, COX-2, BACE-1, and GSK-3β: Computational and In Vivo Studies.Molecules (Basel, Switzerland) · 2024Article
- Systemic Modulators: Potential Mechanism for the 5-HT System to Mediate Exercise Amelioration in Alzheimer's Disease.Aging and disease · 2024Review
- Transcriptional Regulation of the Human 5-HT1A Receptor Gene by Lithium: Role of Deaf1 and GSK3β.International journal of molecular sciences · 2023Article
- The modulatory effects of alkaloid extracts of Cannabis sativa, Datura stramonium, Nicotiana tabacum and male Carica papaya on neurotransmitter, neurotrophic and neuroinflammatory systems linked to anxiety and depression.Inflammopharmacology · 2022Article
- The role of serotonin neurotransmission in rapid antidepressant actions.Psychopharmacology · 2022Review
- Multiple cholinesterase inhibitors have antidepressant-like properties in the mouse forced swim test.Behavioural brain research · 2021Article
- Involvement of 5-Hydroxytryptamine Receptor 2A in the Pathophysiology of Medication-Overuse Headache.Journal of pain research · 2021Article
- Glycogen synthase kinase-3 signaling in cellular and behavioral responses to psychostimulant drugs.Biochimica et biophysica acta. Molecular cell research · 2020Review
- The cholinesterase inhibitor donepezil has antidepressant-like properties in the mouse forced swim test.Translational psychiatry · 2020Article
- GSK3β: A Master Player in Depressive Disorder Pathogenesis and Treatment Responsiveness.Cells · 2020Review
- Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes, BDNF, and astrocytes.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2020Article
- The pivotal role of glycogen synthase kinase 3 (GSK-3) in vomiting evoked by specific emetogens in the least shrew (Cryptotis parva).Neurochemistry international · 2020Article
- Role of Serotonergic System in the Antidepressant Actions of mGlu2/3 Receptor Antagonists: Similarity to Ketamine.International journal of molecular sciences · 2019Review
- Absence of Stress Response in Dorsal Raphe Nucleus in Modulator of Apoptosis 1-Deficient Mice.Molecular neurobiology · 2019Article
- Overcoming Resistance to Selective Serotonin Reuptake Inhibitors: Targeting Serotonin, Serotonin-1A Receptors and Adult Neuroplasticity.Frontiers in neuroscience · 2019Review
- Fluoxetine Inhibits Natural Decay of Long-Term Memory via Akt/GSK-3β Signaling.Molecular neurobiology · 2018Article
- Role of 5-HT1A Receptor Stimulation in the Medial Prefrontal Cortex in the Sustained Antidepressant Effects of Ketamine.The international journal of neuropsychopharmacology · 2018Article
- Modulation of Synaptic Plasticity in the Cortex Needs to Understand All the Players.Frontiers in synaptic neuroscience · 2017Review
- Narcolepsy-like sleep disturbance in orexin knockout mice are normalized by the 5-HT1A receptor agonist 8-OH-DPAT.Psychopharmacology · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Serotonin modulates brain physiology and behavior and has major roles in brain diseases involving abnormal mood and cognition. Enhancing brain serotonin has been found to regulate glycogen synthase Kinase-3 (GSK3), but the signaling mechanism and functional significance of this regulation remain to be determined. In this study, we tested the signaling mechanism mediating 5-HT1A receptor-regulated GSK3 in the hippocampus. Using mutant GSK3 knock-in mice, we also tested the role of GSK3 in the behavioral effects of 5-HT1A receptors and the serotonin reuptake inhibitor fluoxetine. The results showed that activation of 5-HT1A receptors by 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) increased phosphorylation of the N-terminal serine of both GSK3α and GSK3β in several areas of the hippocampus. The effect of 8-OH-DPAT was accompanied by an increase in the active phosphorylation of Akt, and was blocked by LY294002, an inhibitor of phosphoinositide 3-kinases (PI3K). Phosphorylation of GSK3β, but not GSK3α, was necessary for 5-HT1A receptors to suppress the hippocampus-associated contextual fear learning. Furthermore, acute fluoxetine treatment up-regulated both phospho-Ser21-GSK3α and phospho-Ser9-GSK3β in the hippocampus. Blocking phosphorylation of GSK3α and GSK3β diminished the anti-immobility effect of fluoxetine treatment in the forced swim test, wherein the effect of GSK3β was more prominent. These results together suggest that PI3K/Akt is a signaling mechanism mediating the GSK3-regulating effect of 5-HT1A receptors in the hippocampus, and regulation of GSK3 is an important intermediate signaling process in the behavioral functions of 5-HT1A receptors and fluoxetine.
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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.