Age-related substantia nigra-mediated seizure facilitation

Reiko Okada; Solomon L. Moshe; Bowen Y. Wong; Ellen F. Sperber; Dayao Zhao

doi:10.1016/0014-4886(86)90157-3

Age-related substantia nigra-mediated seizure facilitation

Reiko Okada, Solomon L. Moshe, Bowen Y. Wong, Ellen F. Sperber, Dayao Zhao

Neurology

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

37 Scopus citations

Abstract

We investigated the role of the GABAergic system of the substantia nigra in seizures of rat pups. Rat pups had bilateral cannulae implanted chronically either in the sub-stantia nigra or 1.5 mm dorsal to it. At age 16 to 17 days, seizures were induced in the cannulated rats and naive (intact) controls by exposure to flurothyl following pretreatment with the GABA agonist, muscimol, or vehicle. Naive rats were the most resistant to flurothyl seizures. Bilateral nigral infusions of muscimol markedly facilitated the development of flurothyl seizures in a dose-response manner and differed significantly from the vehicle controls or rats infused with muscimol dorsally to the substantia nigra. In contrast, bilateral nigral muscimol infusions protected adult rats against the development of flurothyl seizures. Our data indicate that the effects of nigral GABA agonist infusions on seizures are age-dependent; the altered responsivity of the GABAergic nigral system in immature rats may be responsible in part for the increased seizure susceptibility of the developing central nervous system.

Original language	English (US)
Pages (from-to)	180-187
Number of pages	8
Journal	Experimental Neurology
Volume	93
Issue number	1
DOIs	https://doi.org/10.1016/0014-4886(86)90157-3
State	Published - Jul 1986

ASJC Scopus subject areas

Neurology
Developmental Neuroscience

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@article{66c4c9ca81284f9782b67f87e9391f03,

title = "Age-related substantia nigra-mediated seizure facilitation",

abstract = "We investigated the role of the GABAergic system of the substantia nigra in seizures of rat pups. Rat pups had bilateral cannulae implanted chronically either in the sub-stantia nigra or 1.5 mm dorsal to it. At age 16 to 17 days, seizures were induced in the cannulated rats and naive (intact) controls by exposure to flurothyl following pretreatment with the GABA agonist, muscimol, or vehicle. Naive rats were the most resistant to flurothyl seizures. Bilateral nigral infusions of muscimol markedly facilitated the development of flurothyl seizures in a dose-response manner and differed significantly from the vehicle controls or rats infused with muscimol dorsally to the substantia nigra. In contrast, bilateral nigral muscimol infusions protected adult rats against the development of flurothyl seizures. Our data indicate that the effects of nigral GABA agonist infusions on seizures are age-dependent; the altered responsivity of the GABAergic nigral system in immature rats may be responsible in part for the increased seizure susceptibility of the developing central nervous system.",

author = "Reiko Okada and Moshe, {Solomon L.} and Wong, {Bowen Y.} and Sperber, {Ellen F.} and Dayao Zhao",

note = "Funding Information: Abbreviations: FE-flurothyl, SN-substantia nigra. r This work was supported in part by grant NS20253 from the National Institutes of Health and a grant from the Epilepsy Foundation of America. We thank Mr. G. Vemice, Anaquest, NJ, for the generous gift of flurothyl (Indoclon) and Ms. Donna Platyan for her help in the preparation of the manuscript. Dr. Okada was on leave from Dept. of Psychiatry, Juntendo University School of Medicine, Tokyo 113, Japan. Dr. Moshe holds appointments in the Departments of Neurology and Pediatrics; please address reprint requests to him.",

year = "1986",

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doi = "10.1016/0014-4886(86)90157-3",

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AU - Moshe, Solomon L.

AU - Wong, Bowen Y.

AU - Sperber, Ellen F.

AU - Zhao, Dayao

N1 - Funding Information: Abbreviations: FE-flurothyl, SN-substantia nigra. r This work was supported in part by grant NS20253 from the National Institutes of Health and a grant from the Epilepsy Foundation of America. We thank Mr. G. Vemice, Anaquest, NJ, for the generous gift of flurothyl (Indoclon) and Ms. Donna Platyan for her help in the preparation of the manuscript. Dr. Okada was on leave from Dept. of Psychiatry, Juntendo University School of Medicine, Tokyo 113, Japan. Dr. Moshe holds appointments in the Departments of Neurology and Pediatrics; please address reprint requests to him.

PY - 1986/7

Y1 - 1986/7

N2 - We investigated the role of the GABAergic system of the substantia nigra in seizures of rat pups. Rat pups had bilateral cannulae implanted chronically either in the sub-stantia nigra or 1.5 mm dorsal to it. At age 16 to 17 days, seizures were induced in the cannulated rats and naive (intact) controls by exposure to flurothyl following pretreatment with the GABA agonist, muscimol, or vehicle. Naive rats were the most resistant to flurothyl seizures. Bilateral nigral infusions of muscimol markedly facilitated the development of flurothyl seizures in a dose-response manner and differed significantly from the vehicle controls or rats infused with muscimol dorsally to the substantia nigra. In contrast, bilateral nigral muscimol infusions protected adult rats against the development of flurothyl seizures. Our data indicate that the effects of nigral GABA agonist infusions on seizures are age-dependent; the altered responsivity of the GABAergic nigral system in immature rats may be responsible in part for the increased seizure susceptibility of the developing central nervous system.

AB - We investigated the role of the GABAergic system of the substantia nigra in seizures of rat pups. Rat pups had bilateral cannulae implanted chronically either in the sub-stantia nigra or 1.5 mm dorsal to it. At age 16 to 17 days, seizures were induced in the cannulated rats and naive (intact) controls by exposure to flurothyl following pretreatment with the GABA agonist, muscimol, or vehicle. Naive rats were the most resistant to flurothyl seizures. Bilateral nigral infusions of muscimol markedly facilitated the development of flurothyl seizures in a dose-response manner and differed significantly from the vehicle controls or rats infused with muscimol dorsally to the substantia nigra. In contrast, bilateral nigral muscimol infusions protected adult rats against the development of flurothyl seizures. Our data indicate that the effects of nigral GABA agonist infusions on seizures are age-dependent; the altered responsivity of the GABAergic nigral system in immature rats may be responsible in part for the increased seizure susceptibility of the developing central nervous system.

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Age-related substantia nigra-mediated seizure facilitation

Abstract

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