Ricerc@Sapienza

Previous studies have shown that injection of the mGlu5 receptor positive allosteric modulator (PAM)
VU0360172 into either the thalamus or somatosensory cortex markedly reduces the frequency of spike-and-wave
discharges (SWDs) in the WAG/Rij model of absence epilepsy. Here we have investigated the effects of
VU0360172 on GABA transport in the thalamus and somatosensory cortex, as possible modes of action underlying
the suppression of SWDs. Systemic VU0360172 injections increase GABA uptake in thalamic synaptosomes

Absence seizures (ASs), the most common form of generalized epilepsy, have significant consequences for patients in the form of impaired attention, mood, and social deficits, and the potential for development into generalized tonic-clonic seizures. Althoughmechanistic hypotheses of these paroxysmal oscillations are incomplete, evidence suggests that an increase in extrasynaptic GABAAreceptor (eGABAAR) mediated tonic inhibition in thalamocortical (TC) neurons is sufficient to generate an AS phenotype in multiple rodent models.