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Introduction: Absence epilepsy is associated with diffuse spike-and-wave discharges (SWD) on the electroencephalogram (EEG). Recent studies have demonstrated that the primary somatosensory cortex is also implicated in the generation of the SWDs. Objective: This study investigated the effects of systemic and local administrations of U-92032 into the brain of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Methods: GAERS animals underwent stereotaxic surgery for the placement of EEG recording electrodes and guide cannulas for U-92032 administration into the lateral ventricle (intracerebroventricular [i.c.v.]), upper lips area (S1Ulp) or barrel field area (S1B) of primary somatosensory cortex. Following 7 days of recovery, electrical activity was recorded continuously for 1 h before and 6 h after intraperitoneal (0.25; 1; 5 mg/kg i.p.) or local U-92032 or dimethyl sulfoxide (DMSO) injections. Results: No changes were detected in the cumulative duration, mean duration, and number of SWDs following i.p. U-92032 injections. Local i.c.v. injections of U-92032 caused a significant decrease in the cumulative duration (i.c.v., 50 and 100 nmol/L), mean duration (i.c.v., 50, 100, and 250 nmol/L), and the number (i.c.v., 250 nmol/L) of SWDs compared to DMSO groups. Intra-cortical (S1Ulp and S1B) U-92032 injections caused a significant decrease in all 3 parameters compared to DMSO groups, as well. Conclusion: Intra-cortical injection of U-92032 caused almost complete removal of SWDs in GAERS and i.c.v. administration resulted in a significant reduction. However, systemic i.p. administration did not cause a significant change with the applied -doses. [ABSTRACT FROM AUTHOR]

First characterized in 1982, the genetic absence epilepsy rat from Strasbourg (GAERS) has emerged as an animal model highly reminiscent of a specific form of idiopathic generalized epilepsy. Both its electrophysiological (spike-and-wave discharges) and behavioral (behavioral arrest) features fit well with those observed in human patients with typical absence epilepsy and required by clinicians for diagnostic purposes. In addition, its sensitivity to antiepileptic drugs closely matches what has been described in the clinic, making this model one of the most predictive. Here, we report how the GAERS, thanks to its spontaneous, highly recurrent and easily recognizable seizures on electroencephalographic recordings, allows to address several key-questions about the pathophysiology and genetics of absence epilepsy. In particular, it offers the unique possibility to explore simultaneously the neural circuits involved in the generation of seizures at different levels of integration, using multiscale methodologies, from intracellular recording to functional magnetic resonance imaging. In addition, it has recently allowed to perform proofs of concept for innovative therapeutic strategies such as responsive deep brain stimulation or synchrotron-generated irradiation based radiosurgery. [ABSTRACT FROM AUTHOR]