Suppressive effects of intranigral injection of muscimol in three models of generalized non-convulsive epilepsy induced by chemical agents.

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.