Biphasic Modulation of Absence Seizures by Lisuride in GAERS: Dissecting the Role of 5-HT2A Receptors
4 affiliations
- 1Neuroscience Division, School of Bioscience, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK
- 2Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, 1649-028 Lisbon, Portugal
- 3College of Medicine, Korea University, Seoul 02841, Republic of Korea
- 4Department of Medical and Surgical Sciences, University of Magna Graecia, 88100 Catanzaro, Italy
Abstract
Serotonergic signalling modulates absence seizures, and activation of 5-HT2A receptors with TCB-2 suppresses spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). We investigated the effects of lisuride, a serotonergic and dopaminergic ligand with low 5-HT2A receptor signalling efficacy, and examined the contribution of these receptors. Spontaneous seizures were recorded in freely moving male GAERS following systemic administration of lisuride (0.1 or 0.5 mg/kg), with or without pretreatment with the 5-HT2A receptor antagonist MDL11,939. Low-dose lisuride produced a modest pro-absence effect, whereas the higher dose produced a biphasic response: early seizure suppression followed by increased seizure activity. MDL11,939 did not abolish the early suppression, but the late increase observed with lisuride alone was not observed following pretreatment. These findings suggest that the early and late responses involve different mechanisms, with 5-HT2A receptors potentially contributing to the later phase. Lisuride’s effects differ from those reported for the potent 5-HT2A receptor TCB-2, consistent with its broader receptor profile. Further work is needed to determine the contribution of its other targets, including dopaminergic receptors.
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BibTeX
@article{venzi2026biphasic,
title = {{Biphasic Modulation of Absence Seizures by Lisuride in GAERS: Dissecting the Role of 5-HT2A Receptors}},
author = {Marcello Venzi and Vincenzo Crunelli and Giuseppe Di Giovanni},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219815},
url = {https://www.mdpi.com/1422-0067/27/21/9815},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Biphasic Modulation of Absence Seizures by Lisuride in GAERS: Dissecting the Role of 5-HT2A Receptors
AU - Marcello Venzi
AU - Vincenzo Crunelli
AU - Giuseppe Di Giovanni
PY - 2026
DA - 2026/11/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219815
UR - https://www.mdpi.com/1422-0067/27/21/9815
AB - Serotonergic signalling modulates absence seizures, and activation of 5-HT2A receptors with TCB-2 suppresses spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). We investigated the effects of lisuride, a serotonergic and dopaminergic ligand with low 5-HT2A receptor signalling efficacy, and examined the contribution of these receptors. Spontaneous seizures were recorded in freely moving male GAERS following systemic administration of lisuride (0.1 or 0.5 mg/kg), with or without pretreatment with the 5-HT2A receptor antagonist MDL11,939. Low-dose lisuride produced a modest pro-absence effect, whereas the higher dose produced a biphasic response: early seizure suppression followed by increased seizure activity. MDL11,939 did not abolish the early suppression, but the late increase observed with lisuride alone was not observed following pretreatment. These findings suggest that the early and late responses involve different mechanisms, with 5-HT2A receptors potentially contributing to the later phase. Lisuride’s effects differ from those reported for the potent 5-HT2A receptor TCB-2, consistent with its broader receptor profile. Further work is needed to determine the contribution of its other targets, including dopaminergic receptors.
SN - 1422-0067
ER -