Age-related differences in the effects of GABA(A) agonists microinjected into rat substantia nigra: Pro- and anticonvulsant actions

D. S. Garant, S. G. Xu, E. F. Sperber, Solomon L. Moshe

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

GABAergic transmission in the substantia nigra pars reticulata (SNR) has an important role in the control of experimental seizures. In the flurothyl seizure model, SNR microinjection of the selective GABA(A) receptor agonist muscimol results in a biphasic dose-response curve in adults: Intermediate doses are anticonvulsant, but high doses have proconvulsant effects. Another GABA(A) agonist, THIP (4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol), also produces anticonvulsant effects at lower doses, whereas higher doses tend to produce a proconvulsant effect. In 16-day-old rat pups, no anticonvulsant but only proconvulsant effects of muscimol occur, and at lower doses than in adults. These data suggest that the immature SNR is significantly more sensitive to the proconvulsant effects of GABA(A) receptor agonists than is the SNR of adults. We hypothesize that the age-related differences in nigral GABAergic response may be due to ontogenic changes in GABA(A)-sensitive neuronal circuits in the SNR.

Original languageEnglish (US)
Pages (from-to)960-965
Number of pages6
JournalEpilepsia
Volume36
Issue number10
DOIs
StatePublished - 1995

Fingerprint

GABA-A Receptor Agonists
Substantia Nigra
Anticonvulsants
Muscimol
Seizures
Flurothyl
Microinjections
gamma-Aminobutyric Acid
Pars Reticulata

Keywords

  • γ-Aminobutyric acid
  • Epilepsy
  • Flurothyl
  • Muscimol
  • Seizures
  • THIP

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Age-related differences in the effects of GABA(A) agonists microinjected into rat substantia nigra : Pro- and anticonvulsant actions. / Garant, D. S.; Xu, S. G.; Sperber, E. F.; Moshe, Solomon L.

In: Epilepsia, Vol. 36, No. 10, 1995, p. 960-965.

Research output: Contribution to journalArticle

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