Thalamic 5-HT2A receptor activation reduces GABA uptake, increases tonic GABAA inhibition and induces absence seizures in Wistar rats.
Neuropharmacology November 1, 2026 Vincenzo Crunelli, Tatiana P Morais, William M Connelly et al.
Serotonin 5-HT2A receptors (5-HT2ARs) in the thalamus increase in expression during development, shifting from interneurons to thalamocortical neurons in the ventrobasal region. Activating these receptors with the agonist TCB-2 reduces GABA uptake and enhances tonic GABAA currents in ventrobasal thalamocortical neurons, an effect absent in δ-subunit GABAA receptor knockout mice and independent of postsynaptic signaling. Bilateral injection of TCB-2 into the ventrobasal thalamus of freely moving rats induces spike-and-wave discharges and behavioral arrest, which are blocked by ethosuximide, indicating absence seizures. The findings suggest that 5-HT2AR signaling can shape thalamocortical dynamics and increase susceptibility to aberrant rhythmic activity.