Age-dependent effects of γ-aminobutyric acid agents on flurothyl seizures

L. Velisek, J. Veliskova, Y. Ptachewich, J. Ortiz, Shlomo Shinnar, Solomon L. Moshe

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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 GABAergic neurotransmission in rats of various ages. Systemic administration of phenobarbital (PB, a drug that enhances GABA(A) 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 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 anticonvulsant activity in 60-day-old rats. CGP 35348 (a GABA(B) receptor antagonist) was proconvulsant in developing rats but not in 60-day- old rats. A novel GABA(B) 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 GABAergic agents are not uniform across the age span. The differences may reflect age-dependent maturational changes of GABA receptor subtypes, differential action of the drugs on pre- and postsynaptic sites and possible non-GABAergic effects.

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

Fingerprint

Flurothyl
Aminobutyrates
Seizures
Anticonvulsants
GABA-B Receptor Antagonists
gamma-Aminobutyric Acid
Pharmaceutical Preparations
GABA-B Receptor Agonists
GABA Agents
GABA-B Receptors
Baclofen
GABA Receptors
GABA-A Receptors
Phenobarbital
Synaptic Transmission
Age Groups

Keywords

  • Development
  • Flurothyl model
  • GABA(A) receptors
  • GABA(B) receptors
  • Rat
  • Seizures

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Age-dependent effects of γ-aminobutyric acid agents on flurothyl seizures. / Velisek, L.; Veliskova, J.; Ptachewich, Y.; Ortiz, J.; Shinnar, Shlomo; Moshe, Solomon L.

In: Epilepsia, Vol. 36, No. 7, 1995, p. 636-643.

Research output: Contribution to journalArticle

Velisek, L. ; Veliskova, J. ; Ptachewich, Y. ; Ortiz, J. ; Shinnar, Shlomo ; Moshe, Solomon L. / Age-dependent effects of γ-aminobutyric acid agents on flurothyl seizures. In: Epilepsia. 1995 ; Vol. 36, No. 7. pp. 636-643.
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