Article date: 1992/8/21
PubMed ID: 1327581
Journal name: Brain research. Developmental brain research (ISSN: 0165-3806)
The substantia nigra gamma-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 facilitates 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.
Author List: Xu S G, Garant D S, Sperber E F, Moshé S L
Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Convulsants; Isoxazoles; Receptors, GABA-A; Flurothyl; gaboxadol;
Mesh terms: Animals; Convulsants/pharmacology; Dose-Response Relationship, Drug; Drug Synergism; Flurothyl; Infusions, Parenteral; Isoxazoles/pharmacology; Male; Rats; Rats, Sprague-Dawley; Receptors, GABA-A/drug effects; Seizures/chemically induced; Substantia Nigra;