Age-specific effects of baclofen on pentylenetetrazol-induced seizures in developing rats

Purpose: To determine whether seizures have age-specific features, we studied the role of gamma-aminobutyric acid(B) (GABA(B)) transmission in rats of various ages (9, 15, 30, and 60 postnatal days). Methods: We used a GABA(B) receptor agonist baclofen (2 or 5 mg/kg intraperitoneally, i.p.) and a GABA(B) receptor antagonist CGP 35348 (100 or 600 mg/kg i.p.) in the pentylenetetrazol (PTZ)-induced model of clonic and tonic-clonic seizures (100 mg/kg subcutaneously, s.c.). Results: Whereas baclofen was anticonvulsant and CGP 35348 proconvulsant in most animals, there were distinct age-related differences in the effectiveness of these drugs and the antagonist had some anticonvulsant activity in adults. Furthermore, the two drugs acting at GABA(B) receptors had a different profile of action in clonic seizures as compared with tonic-clonic seizures. Conclusions: The differences in the age-specific action of the GABA(B) agonist and antagonist suggest that different GABA(B) receptor subsets may mediate the drug effects. The results indicate that putative antiepileptic drugs (AEDs) must be tested during development because it may not be possible to extrapolate age-specific anticonvulsant effects from studies in adult animals.