The action of a
GABA(B) antagonist
CGP 35348 and a
GABA(B) agonist
baclofen was studied in two models of epileptic
seizures characterized by EEG spike-and-wave rhythm in freely moving immature rats. Rhythmic
metrazol activity (RMA, model of human absences) was induced by low systemic dose of
pentylenetetrazol (PTZ) in 18- and 25-day-old rats, epileptic after discharges (ADs, model of human
myoclonic seizures) were elicited by electrical stimulation of sensorimotor cortex in rat pups 12, 18, and 25 days old.
CGP 35348 (50, 100 and 200 mg/kg i.p.) suppressed RMA in both age groups in a dose-dependent manner. Simultaneously it increased the incidence of
clonic seizures, potentiating thus an effect of PTZ.
Baclofen (1, 3 and 6 mg/kg i.p.) augmented markedly RMA in 25-day-old rats. On the contrary,
baclofen suppressed RMA in a part of 18-day-old animals. Incidence of
seizures was not changed by
baclofen in either age group. As ADs are concerned
CGP 35348 (100 and 200 mg/kg i.p.) exhibited a proconvulsant action,
baclofen (3, 6 or 12 mg/kg i.p.) was
anticonvulsant, but again an irregularity of action was found in 18-day-old rats. The role of
GABA(B)-mediated inhibition in epileptogenesis depends on the type of
seizures and also on the stage of maturation.