THE ROLE OF GABA(B) RECEPTOR ACTIVATION IN ABSENCE SEIZURES OF LETHARGIC (IH/IH) MICE

Lethargic (lh/lh) mice, which function as an animal model of absence seizures, have spontaneous seizures that have behavioral and electrographic features and anticonvulsant sensitivity similar to those of human absence seizures. Antagonists of the gamma-aminobutyric acid(B) (GABA(B)) receptor suppressed these seizures in lethargic mice, whereas agonists of GABA(B) receptors exacerbated them. Furthermore, GABA(B) receptor binding and synaptically evoked GABA(B) receptor-mediated inhibition of N-methyl-D-aspartate responses were selectively increased in lh/lh mice. Therefore, enhanced GABA(B) receptor-mediated synaptic responses may underlie absence seizures in lh/lh mice, and GABA(B) receptor antagonists hold promise as anticonvulsants for absence seizures.