Co-expression and In Vivo Interaction of Serotonin1A and Serotonin2A Receptors in Pyramidal Neurons of Prefrontal Cortex
Abstract
The prefrontal cortex plays a key role in the control of higher brain functions and is involved in the pathophysiology and treatment of schizophrenia. Here we report that approximately 60% of the neurons in rat and mouse prefrontal cortex express 5-HT(1A) and/or 5-HT2A receptor mRNAs, which are highly co-localized (approximately 80%). The electrical stimulation of the dorsal and median raphe nuclei elicited 5-HT1A-mediated inhibitions and 5-HT2A-mediated excitations in identified pyramidal neurons recorded extracellularly in rat medial prefrontal cortex (mPFC). Opposite responses in the same pyramidal neuron could be evoked by stimulating the raphe nuclei at different coordinates, suggesting a precise connectivity between 5-HT neuronal subgroups and 5-HT1A and 5-HT2A receptors in pyramidal neurons. Microdialysis experiments showed that the increase in local 5-HT release evoked by the activation of 5-HT2A receptors in mPFC by DOI (5-HT2A/2C receptor agonist) was reversed by co-perfusion of 5-HT1A agonists. This inhibitory effect was antagonized by WAY-100635 and the prior inactivation of 5-HT1A receptors in rats and was absent in mice lacking 5-HT1A receptors. These observations help to clarify the interactions between the mPFC and the raphe nuclei, two key areas in psychiatric illnesses and improve our understanding of the action of atypical antipsychotics, acting through these 5-HT receptors.
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In rodents, the 5-HT2A receptor expression pattern has been confirmed using immunohistochemistry, light and electron microscope immunocytochemistry, in situ hybridization, receptor autoradiography, and transgenic mice expressing EGFP under control of the 5-HT2A receptor promoter.
“In rodents, this expression pattern has been confirmed using immunohistochemistry (203–206), light and electron microscope immunocytochemistry (203), in situ hybridization (207, 208), receptor autoradiography (209), and transgenic mice expressing EGFP under control of the 5-HT2A receptor promoter (210).”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [207]
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- Authors
- Amargos-Bosch, M.
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-03-01
- Volume
- 14
- Issue
- 3
- Pages
- 281-299
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2135447632
- Cited by
- 370
- References
- 3
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 15 · 2023: 11 · 2022: 7 · 2021: 15 · 2020: 9 · 2019: 7 · 2018: 10 · 2017: 15 · 2016: 17 · 2015: 24 · 2014: 17 · 2013: 21 · 2012: 22
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- 5-HT1A receptor, 5-HT2A receptor, receptor colocalization, medial prefrontal cortex, pyramidal neurons, raphe nuclei, serotonin release, digital object identifiers, WAY-100635, atypical antipsychotics, schizophrenia, receptor interaction, gene expression
- MeSH terms
- Amphetamines, Animals, Autoradiography, Dopamine, Electric Stimulation, Male, Mice, Inbred C57BL, Raphe Nuclei, RNA, Messenger, Serotonin, Rats, Wistar, Serotonin Receptor Agonists, Prefrontal Cortex, In Situ Hybridization, Microdialysis, Ventral Tegmental Area, Pyramidal Cells, Mice, Knockout, Receptor, Serotonin, 5-HT1A, Receptor, Serotonin, 5-HT2A, Mice, Rats
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