ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
This article is part of the Research TopicAdvances in Neuropharmacological Therapies: From Molecular Discoveries to Personalized Clinical ApplicationsView all 8 articles
Thalamic Distribution and Effects of 5-HT2C Receptors on Tonic GABAA Inhibition and Absence Seizures: Implications for Treatment
Provisionally accepted
- 1Neuroscience Division, School of Bioscience, Cardiff Univeristy,, Cardiff, United Kingdom
- 2Universita degli Studi di Bologna Dipartimento di Scienze Mediche Veterinarie, Ozzano dell'Emilia, Italy
- 3Physiology and Biochemistry, Department of Medical and Surgical Science, University of Magna Graecia, Catanzaro, Italy
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Childhood absence epilepsy (CAE) is associated with enhanced GABAergic function in the ventrobasal (VB) thalamus, with increased tonic GABAA current in thalamocortical (TC) neurons. Serotonin (5-HT) modulates epilepsy, including CAE, and 5-HT2CR activation exhibits anti-absence seizure (AS) effects, though its cellular mechanisms remain unclear. Here, we investigated the thalamic distribution of 5-HT2CRs with immunohistochemistry and studied how their activation affects and tonic GABAA currents in TC neurons of Wistar rats, Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well-validated AS model, and their non-epileptic control strain (NEC). We also recorded the effect of systemic injection of a 5-HT2CR agonist Ro 60-0175 on ASs in freely moving GAERS rats. No differences were observed in 5-HT2CR expression in the nucleus reticularis thalami (NRT), the main source of GABAergic afferents to the VB. In contrast, 5-HT2CR expression was lowest in the GAERS VB and highest in Wistar compared to NEC VB. The 5-HT2CR agonist Ro 60-0175, induced an anti-absence effect in adult GAERS. TC neurons in Wistar and NEC rats exhibited similar lower tonic GABAA currents compared to GAERS rats, and 5-HT2CR activation with Ro 60-0175 reduced the tonic GABAA currents in all strains. These findings suggest that 5-HT2CRs regulate thalamic tonic GABAA inhibition, and their anti-absence effects indicate that they may represent a potential therapeutic target.
Keywords: GAERS rats, Nucleus reticularis thalami, Ro 60-0175, SB242084, spike-and-wave discharges, thalamocortical neurons, ventrobasal complex
Received: 21 Oct 2025; Accepted: 28 Jan 2026.
Copyright: © 2026 Cavaccini, Venzi, Bombardi, Crunelli and Di Giovanni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Giuseppe Di Giovanni
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