AGE-DEPENDENT EFFECTS OF GAMMA-AMINOBUTYRIC-ACID AGENTS ON FLUROTHYL SEIZURES

Behavioral characteristics of seizures have age-dependent features, wh ich suggests that effective treatment of seizures may be age-specific as well. In experiments that used the flurothyl seizure model, we exam ined the effects of several drugs that affect GABAergic neurotransmiss ion in rats of various ages. Systemic administration of phenobarbital (PB, a drug that enhances GABA(A) receptor-mediated inhibition) was an ticonvulsant in most age groups. In contrast, gamma-vinyl GABA (VGB, a drug that increases endogenous GABA levels and enhances both GABA(A) and GABA(B) receptor transmission) did not have anticonvulsant effects . Baclofen (a GABA(B) receptor agonist) was proconvulsant in 9-day-old rat pups, and anticonvulsant in 15-30-day-old rats and lost its antic onvulsant activity in 60-day-old rats. CGP 35348 (a GABA(B) receptor a ntagonist) was proconvulsant in developing rats but not in 60-day-old rats. A novel GABA(B) receptor antagonist, CGP 36742, was proconvulsan t in 9- and 15-day-old rats but had no effects in 30- and 60-day-old r ats. These results indicate that the effects of presumed GABAergic age nts are not uniform across the age span. The differences may reflect a ge-dependent maturational changes of GABA receptor subtypes, different ial action of the drugs on pre- and postsynaptic sites and possible no n-GABAergic effects.