THE ROLE OF GABA(B) MECHANISMS IN ANIMAL-MODELS OF ABSENCE SEIZURES

Generalized absence seizures in humans are a unique type of epilepsy c haracterized by a synchronous, bilateral 3-Hz spike and wave discharge emanating from a cortical and thalamic network within the brain. The availability of a number of pharmacological and genetic animal models has provided us with the means with which to investigate the cellular and molecular mechanisms underlying these seizures. Over the last few years a significant amount of research in these models has focused on the role of the inhibitory GABA(B) receptors, which have been previous ly described in a number of brain areas as being responsible for a lon g-lasting hyperpolarization and depression in neurotransmitter release . Initial studies provided evidence that the GABA(B) receptor was capa ble of generating the low threshold calcium spike required for initiat ion of the burst firing, leading researchers to hypothesize that the G ABA(B) receptors played a significant role in these seizures. Subseque nt research took advantage of the new generation of GABA(B) antagonist s that became available in the early 1990s and demonstrated that in a number of models the seizures could be abolished by the administration of one of these compounds. Further biochemical, molecular, and electr ophysiological experiments have been carried out to determine the exac t involvement of GABA(B) receptors and their mechanism of action. The current evidence and interpretations of this work are presented here.