THALAMIC NMDA TRANSMISSION IN A GENETIC MODEL OF ABSENCE EPILEPSY IN RATS

In the selected strain of GAERS Wistar rats (Genetic Absence Epilepsy Rats from Strasbourg), all animals present spontaneously recurrent abs ence seizures characterized by bilateral and synchronous generalized s pike-and-wave discharges (SWD) accompanied by behavioural arrest. SWD depend on a thalamo-cortical network connecting the reticular and rela y nuclei of the thalamus and their cortical projection areas; This loo p involves both GABAergic and glutamatergic synapses. In the present s tudy, we investigated the implication of NMDA transmission in the gene sis of absence seizures in GAERS. Intra-peritoneal or intra-cerebroven tricular injections of NMDA, the competitive NMDA antagonist CGP 40116 , the non-competitive NMDA antagonist (+)-MK 801 and the antagonist of the glycine modulatory site 5,7-dichlorokynurenic acid dose-dependent ly suppressed SWD. Bilateral infusions of the same drugs in the latera l relay nuclei of the thalamus had similar suppressive effects. Intra- cerebroventricular or intrathalamic administration of D-serine, an ago nist of the glycine modulatory site, had no effect on SWD. These data show that NMDA neurotransmission, especially within the thalamus, play s a major role in the control of absence seizures in GAERs. Disregulat ion of NMDA-mediated transmission by NMDA or antagonists, interacting with various sites of the receptor complex, may suppress the thalamo-c ortical oscillatory activity which underlies SWD.