EVIDENCE FOR GABA(B)-MEDIATED MECHANISMS IN EXPERIMENTAL GENERALIZED ABSENCE SEIZURES

Experimental absence seizures are characterized by the fact that they are exacerbated by both direct and indirect GABA agonists. To date most of the studies that have examined this phenomenon have utilized GABA(A) agonists. We assessed the effect of a GABA(B) agonist, baclofen and a specific GABA(B) antagonist in two pharmacologic models of absence seizures in rodent after using either gamma-hydroxybutyrate or pentylenetetrazole to induce the bilaterally synchronous spike wave discharges that typify absence seizures in rodent. Baclofen markedly prolonged and the GABA(B) antagonist attenuated or blocked the experimental absence seizures in both models. These data suggest a role for GABA(B)-related mechanisms in the pathogenesis of generalized absence seizures and raise the possibility that GABA(B) antagonists may have therapeutic potential as antiabsence drugs.