Ricerc@Sapienza

Absence epilepsy and depression are comorbid disorders, but the molecular link between the two disorders is unknown. Here, we examined the role of the melatoninergic system in the pathophysiology of spike and wave discharges (SWDs) and depression-like behaviour in the Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat model of absence epilepsy. In WAG/Rij rats, SWD incidence was higher during the dark period of the light-dark cycle, in agreement with previous findings.

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.

Introduction: Several drugs targeting the GABAergic system are used in the treatment of epilepsy, but only one drug targeting glutamate receptors is on the market. This is surprising because an imbalance between excitatory and inhibitory neurotransmission lies at the core of the pathophysiology of epilepsy. One possible explanation is that drug development has been directed towards the synthesis of molecules that inhibit the activity of ionotropic glutamate receptors.