The proconvulsant effect of nigral infusions of THIP on flurothyl-induced seizures in rat pups

S. G. Xu; D. S. Garant; E. F. Sperber; S. L. Moshé

doi:10.1016/0165-3806(92)90070-D

The proconvulsant effect of nigral infusions of THIP on flurothyl-induced seizures in rat pups

S. G. Xu, D. S. Garant, E. F. Sperber, S. L. Moshé

Neurology

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

The substantia nigra γ-aminobutyric acid (GABA) system is crucial for seizure control. Our previous work indicates that in 16-day-old rat pups, nigral administration of the GABA_A receptor agonist muscimol facilities flurothyl-induced seizures, whereas it suppresses seizures in adult rats. To determine whether the proconvulsant effect of muscimol in rat pups may be mediated by nigral GABA_A receptors, in the present study we applied a selective GABA_A receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). Bilateral nigral infusions of THIP (500 or 700 ng) significantly decreased the thresholds for flurothyl seizures in a dose-dependent fashion. Doses of 350 ng or less did not significantly modify the susceptibility to seizures. An anticonvulsant action of THIP could not be detected at any dose. Administration of an effective THIP dose (500 ng) 2 mm dorsal to the SNR had no influence on seizures. These findings suggest that in rat pups the proconvulsant effect of nigral GABA_A receptor agonists may be attributed to unique pharmacologic characteristics of GABA_A receptors during development.

Original language	English (US)
Pages (from-to)	275-277
Number of pages	3
Journal	Developmental Brain Research
Volume	68
Issue number	2
DOIs	https://doi.org/10.1016/0165-3806(92)90070-D
State	Published - Aug 21 1992

Keywords

Convulsion
Rat
Seizure
Substantia nigra
THIP
γ-aminobutyric acid

ASJC Scopus subject areas

Developmental Neuroscience
Developmental Biology

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10.1016/0165-3806(92)90070-D

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title = "The proconvulsant effect of nigral infusions of THIP on flurothyl-induced seizures in rat pups",

abstract = "The substantia nigra γ-aminobutyric acid (GABA) system is crucial for seizure control. Our previous work indicates that in 16-day-old rat pups, nigral administration of the GABAA receptor agonist muscimol facilities flurothyl-induced seizures, whereas it suppresses seizures in adult rats. To determine whether the proconvulsant effect of muscimol in rat pups may be mediated by nigral GABAA receptors, in the present study we applied a selective GABAA receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). Bilateral nigral infusions of THIP (500 or 700 ng) significantly decreased the thresholds for flurothyl seizures in a dose-dependent fashion. Doses of 350 ng or less did not significantly modify the susceptibility to seizures. An anticonvulsant action of THIP could not be detected at any dose. Administration of an effective THIP dose (500 ng) 2 mm dorsal to the SNR had no influence on seizures. These findings suggest that in rat pups the proconvulsant effect of nigral GABAA receptor agonists may be attributed to unique pharmacologic characteristics of GABAA receptors during development.",

keywords = "Convulsion, Rat, Seizure, Substantia nigra, THIP, γ-aminobutyric acid",

author = "Xu, {S. G.} and Garant, {D. S.} and Sperber, {E. F.} and Mosh{\'e}, {S. L.}",

note = "Funding Information: Supported by NIH Grant NS-20253 and NRSA training Grant MH-15788 from the NIMH.",

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AU - Moshé, S. L.

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The proconvulsant effect of nigral infusions of THIP on flurothyl-induced seizures in rat pups

Abstract

Keywords

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