ArticleThe Journal of biological chemistry2008
Activation of 5-HT2A/C receptors counteracts 5-HT1A regulation of n-methyl-D-aspartate receptor channels in pyramidal neurons of prefrontal cortex.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 125 citations in OpenAlex.
- Serotonergic modulation of excitatory synapse development and plasticity.Molecules and cells · 2026Review
- Single-dose psilocybin promotes cell-type-specific changes of neurons in the orbitofrontal cortex.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Advances in the Treatment of Cognitive Impairment in Schizophrenia: Targeting NMDA Receptor Pathways.International journal of molecular sciences · 2024Review
- Review
- 5-HTInternational journal of molecular sciences · 2024Article
- A Comprehensive Review of the Current Status of the Cellular Neurobiology of Psychedelics.Biology · 2023Review
- A molecular analysis of substituted phenylethylamines as potential microtubule targeting agents through in silico methods and in vitro microtubule-polymerization activity.Scientific reports · 2023Article
- A Postsynaptic Density Immediate Early Gene-Based Connectome Analysis of Acute NMDAR Blockade and Reversal Effect of Antipsychotic Administration.International journal of molecular sciences · 2023Article
- Interactions between β-arrestin proteins and the cytoskeletal system, and their relevance to neurodegenerative disorders.Frontiers in endocrinology · 2023Review
- Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications.Molecular psychiatry · 2022Review
- G-protein coupled receptors and synaptic plasticity in sleep deprivation.World journal of psychiatry · 2021Review
- Investigation of the Role of Stimulation and Blockade of 5-HTJournal of molecular neuroscience : MN · 2021Article
- Modulation of NMDA Receptors by G-protein-coupled receptors: Role in Synaptic Transmission, Plasticity and Beyond.Neuroscience · 2021Review
- Sucrose Consumption Alters Serotonin/Glutamate Co-localisation Within the Prefrontal Cortex and Hippocampus of Mice.Frontiers in molecular neuroscience · 2021Article
- Contribution of serotonin receptor subtypes to hallucinogenic activity of 25I-NBOMe and to its effect on neurotransmission.Pharmacological reports : PR · 2020Article
- Upregulated 5-HTMolecular brain · 2020Article
- Serotonin receptors 2A and 1A modulate anxiety-like behavior in post-traumatic stress disordered mice.American journal of translational research · 2019Article
- CaMello-XR enables visualization and optogenetic control of GCommunications biology · 2019Article
- The Neuroprotective Effects of Exercise: Maintaining a Healthy Brain Throughout Aging.Brain plasticity (Amsterdam, Netherlands) · 2018Review
- Fenfluramine diminishes NMDA receptor-mediated seizures via its mixed activity at serotonin 5HT2A and type 1 sigma receptors.Oncotarget · 2018Article
1 more citing papers are in PubMed but not listed here.
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5 authors at 1 institution in 1 country.
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Abstract
Abnormal serotonin-glutamate interaction in prefrontal cortex (PFC) is implicated in the pathophysiology of many mental disorders, including schizophrenia and depression. However, the mechanisms by which this interaction occurs remain unclear. Our previous study has shown that activation of 5-HT(1A) receptors inhibits N-methyl-D-aspartate (NMDA) receptor (NMDAR) currents in PFC pyramidal neurons by disrupting microtubule-based transport of NMDARs. Here we found that activation of 5-HT(2A/C) receptors significantly attenuated the effect of 5-HT(1A) on NMDAR currents and microtubule depolymerization. The counteractive effect of 5-HT(2A/C) on 5-HT(1A) regulation of synaptic NMDAR response was also observed in PFC pyramidal neurons from intact animals treated with various 5-HT-related drugs. Moreover, 5-HT(2A/C) stimulation triggered the activation of extracellular signal-regulated kinase (ERK) in dendritic processes. Inhibition of the beta-arrestin/Src/dynamin signaling blocked 5-HT(2A/C) activation of ERK and the counteractive effect of 5-HT(2A/C) on 5-HT(1A) regulation of NMDAR currents. Immunocytochemical studies showed that 5-HT(2A/C) treatment blocked the inhibitory effect of 5-HT(1A) on surface NR2B clusters on dendrites, which was prevented by cellular knockdown of beta-arrestins. Taken together, our study suggests that serotonin, via 5-HT(1A) and 5-HT(2A/C) receptor activation, regulates NMDAR functions in PFC neurons in a counteractive manner. 5-HT(2A/C), by activating ERK via the beta-arrestin-dependent pathway, opposes the 5-HT(1A) disruption of microtubule stability and NMDAR transport. These findings provide a framework for understanding the complex interactions between serotonin and NMDARs in PFC, which could be important for cognitive and emotional control in which both systems are highly involved.
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