Article date: 1989/9/25
PubMed ID: 2551457
Journal name: Brain research (ISSN: 0006-8993)
The involvement of intranigral gamma-aminobutyric acid (GABA) receptors in the control of generalized non-convulsive epilepsy was investigated in the rat in 3 models of petit mal epilepsy induced by systemic administration of gamma-butyrolactone, pentylenetetrazol and 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin 3-ol (THIP). Bilateral intranigral injection of muscimol (2 ng/0.2 microliters/side), a GABAA receptor agonist, significantly reduced the duration of EEG-recorded spike-and-wave discharges induced by gamma-butyrolactone (100 and 200 mg/kg i.p.), pentylenetetrazol (20 mg/kg i.p.) and THIP (7.5 mg/kg i.p.). This treatment had no effect on the electroencephalographic discharges observed after injection of THIP (10 mg/kg i.p.). Bilateral injection of muscimol (2 and 4 ng/side) into the substantia nigra did not modify the latency of onset nor the duration of clonic seizures induced by pentylenetetrazol at the dose of 40 mg/kg i.p. Bipolar depth electrode recording indicated that intranigral injection of muscimol did not alter nigral electroencephalographic activity. Autoradiography following intranigral injection of [3H]muscimol indicated a diffusion not exceeding 400 microns from the injection site. These results confirm that activation of GABA receptors in the substantia nigra suppresses the occurrence of spike-and-wave discharges in animal models of generalized non-convulsive epilepsy.
Author List: Depaulis A, Snead O C, Marescaux C, Vergnes M
Publication Types: Journal Article; Research Support, Non-U.S. Gov't
Substances mentioned in the article: Convulsants; Isoxazoles; Receptors, GABA-A; Muscimol; gamma-Aminobutyric Acid; gaboxadol; 4-Butyrolactone; Pentylenetetrazole;
Mesh terms: 4-Butyrolactone; Animals; Convulsants/pharmacology; Electroencephalography; Epilepsy/chemically induced; Isoxazoles; Male; Muscimol/pharmacology; Pentylenetetrazole; Rats; Rats, Inbred Strains; Receptors, GABA-A/drug effects; Substantia Nigra/drug effects; gamma-Aminobutyric Acid/metabolism;