The Ontogeny of GABAergic Enhancement of the γ-Hydroxybutyrate Model of Generalized Absence Seizures

The ontogeny of GABAergic enhancement of generalized absence seizures was examined in the gamma-hydroxybutyrate (GHB) model of generalized absence seizures. The GHB seizure was quantitated in developing and adult rats in the presence of varying doses of the GABAa agonist muscimol or intracerebroventricularly (i.c.v.) administered GABA. Both GABA and muscimol potentiated GHB-induced seizures in an age-dependent fashion. The adult dose of 1 mg/kg muscimol was extremely potent in rats less than 28 days of age and resulted in the death of all younger animals tested secondary to profound hypothermia. A dose of 0.1 mg/kg muscimol was associated with a significant prolongation of GHB seizure in rats less than 35 days of age, but had no effect on older animals. The response to GHB was also age dependent, with the greatest sensitivity occurring during the fourth and fifth week of life. The developmental sensitivity of the rat to GHB seizure correlated with enhancement of the seizure by muscimol and GABA, and both phenomena parallel the maturation of thalamocortical recruiting mechanisms thought to play a role in the pathogenesis of the bilaterally synchronous spike wave discharges that characterize generalized absence seizures.