Lack of proconvulsant action of GABA depletion in substantia nigra in several seizure models.
The effect of intranigral application of a gamma-aminobutyric acid (GABA) synthesis inhibitor, was examined in 3 different rat seizure models. Bilateral intranigral infusion of isoniazid (150 micrograms) did not potentiate the effect of subcutaneous administration of a threshold dose (1.5 mg/kg) of the GABA antagonist bicuculline. Similarly, following pretreatment with intranigral isoniazid, neither severity nor latency to onset of seizures elicited by systemic injection of kainic acid (9 mg/kg) were modified. In addition, convulsive seizures evoked by the focal injection of bicuculline methiodide (40 ng) in an epileptogenic site within the deep prepiriform cortex (area tempestas) were not potentiated by intranigral isoniazid. These results were in sharp contrast to the marked potentiating effect of intranigral isoniazid (150 or 85 micrograms) on seizures induced by systemic administration of a subconvulsant dose of pilocarpine (150 mg/kg). In addition, we attempted to evoke a proconvulsant action from striatum. The striatum, origin of GABAergic projections to substantia nigra, is a region in which application of GABA antagonists have been found to be anticonvulsant in several seizure models. We therefore examined the effect of bilateral intrastriatal infusion of the GABA agonist, muscimol (5 ng) on the convulsant effect of threshold doses of systemically administered bicuculline (1.5 mg/kg). As was true with intranigral isoniazid, no proconvulsant effect was found using intrastriatal muscimol. Our data demonstrate that whereas striatonigral GABA circuitry can be activated by exogenous treatments so as to produce anticonvulsant actions in most seizure models, suppression of this circuitry does not potentiate convulsant activity in many of the same models.
Maggio
R
R
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007.
Sohn
E
E
Gale
K
K
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002540:Cerebral Cortex / Q000502:physiology; D007538:Isoniazid / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000503:physiopathology*; D013378:Substantia Nigra / Q000033:anatomy & histology / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D010862:Pilocarpine; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D007608:Kainic Acid; D007538:Isoniazid; D001640:Bicuculline