Age‐Dependent Effects of γ‐Aminobutyric Acid Agents on Flurothyl Seizures

Libor Velíšek, Jana Velíšková, Yael Ptachewich, José Ortíz, Shlomo Shinnar, Solomon L. Moshé

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Summary: Behavioral characteristics of seizures have age‐dependent features, which suggests that effective treatment of seizures may be age‐specific as well. In experiments that used the flurothyl seizure model, we examined the effects of several drugs that affect GAB Aergic neurotransmission in rats of various ages. Systemic administration of phenobarbital (PB, a drug that enhances GABA, receptor‐mediated inhibition) was anticonvulsant in most age groups. In contrast, γ‐ vinyl GABA (VGB, a drug that increases endogenous GABA levels and enhances both GABAA and GABAB, receptor transmission) did not have anticonvulsant effects. Baclofen (a GABAB receptor agonist) was proconvulsant in 9‐day‐old rat pups, and anticonvulsant in 15–30‐day‐old rats and lost its anticonvulsant activity in 60‐day‐old rats. CGP 35348 (a GABAB receptor antagonist) was proconvulsant in developing rats but not in 60‐day‐old rats. A novel GABA, receptor antagonist, CGP 36742, was proconvulsant in 9‐ and 15‐day‐old rats but had no effects in 30‐ and 60‐day‐old rats. These results indicate that the effects of presumed GAB Aergic agents are not uniform across the age span. The differences may reflect age‐dependent maturational changes of GAB A receptor subtypes, differential action of the drugs on pre‐ and postsynaptic sites and possible non‐GAB Aergic effects.

Original languageEnglish (US)
Pages (from-to)636-643
Number of pages8
JournalEpilepsia
Volume36
Issue number7
DOIs
StatePublished - Jul 1995

Keywords

  • Development
  • Flurothyl model
  • GABA, receptors
  • GABA, receptors
  • Rat
  • Seizures

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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