The role of GABA(B) mechanisms in animal models of absence seizures

Generalized absence seizures in humans are a unique type of epilepsy characterized 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 previously described in a number of brain areas as being responsible for a long-lasting hyperpolarization and depression in neurotransmitter release. Initial studies provided evidence that the GABA(B) receptor was capable of generating the low threshold calcium spike required for initiation of the burst firing, leading researchers to hypothesize that the GABA(B) receptors played a significant role in these seizures. Subsequent research took advantage of the new generation of GABA(B) antagonists 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 electrophysiological experiments have been carried out to determine the exact involvement of GABA(B) receptors and their mechanism of action. The current evidence and interpretations of this work are presented here.