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: W e used a GABA(B) receptor agonist baclofen (2 or 5 mg/kg intraperitone ally, 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 t onic-clonic seizures (100 mg/kg subcutaneously, s.c.). Results: Wherea s baclofen was anticonvulsant and CGP 35348 proconvulsant in most anim als, 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 d ifferent profile of action in clonic seizures as compared with tonic-c lonic seizures. Conclusions: The differences in the age-specific actio n of the GABA(B) agonist and antagonist suggest that different GABA(B) receptor subsets may mediate the drug effects. The results indicate t hat putative antiepileptic drugs (AEDs) must be tested during developm ent because it may not be possible to extrapolate age-specific anticon vulsant effects from studies in adult animals.