Is the anticonvulsant effect of substantia nigra infusion of gamma-vinyl-GABA (GVG) mediated by the GABAA receptor in rat pups?

S. G. Xu, E. F. Sperber, S. L. Moshé

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The substantia nigra GABAergic system is considered important for the modification of seizures. Our previous studies have shown that, in rat pups, nigral infusions of baclofen suppressed flurothyl-induced seizures. In the present study, we determined, in rat pups, the effect of nigral infusions of γ-vinyl-GABA (GVG) on clonic-tonic seizures induced by flurothyl, generated a dose-response curve of the GVG effect and investigated the possible role of the nigral GABAA receptor in mediating the GVG effect. Bilateral nigral infusions of GVG profoundly suppressed flurothyl-induced tonic seizures in a dose-dependent fashion. Flurothyl-induced clonic seizures were not modified. The lowest effective dose of nigral GVG administration was 5 μg/0.25 μl per site. Nigral infusions of GVG at doses greater than 10 μg/0.25 μl induced sedation as well. Infusions of GVG, 2 mm dorsal to the substantia nigra, did not alter seizure latencies. Bilateral nigral infusions of bicuculline, a specific GABAA receptor antagonist, reduced the protective potency of GVG against flurothyl-induced seizures. Nigrally administered muscimol, a GABAA receptor agonist, also attenuated the anticonvulsant effect of GVG. These findings suggest that the optimal dose of nigrally infused GVG against flurothyl-induced seizures is in the range of 5-10 μg/0.25 μl and that GVG may be more efficient as an anticonvulsant for the treatment of tonic seizures in developing animals. The anticonvulsant effect of GVG may, in part, involve the nigral GABAA receptor. The data, together with the previous experiments, indicate that both nigral GABAA and GABAB receptors may play a role in the regulation of seizures in rat pups. The possible mechanisms through which nigrally infused muscimol reduced the action of GVG are discussed.

Original languageEnglish (US)
Pages (from-to)17-21
Number of pages5
JournalDevelopmental Brain Research
Volume59
Issue number1
DOIs
StatePublished - Mar 18 1991

Keywords

  • Bicuculline
  • Development
  • Gamma-vinyl-GABA
  • Muscimol
  • Rat
  • Seizure
  • Substantia nigra

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology

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