Substantia nigra: site of anticonvulsant activity mediated by gamma-aminobutyric acid

Abstract

Localization of the anatomic substrate for anticonvulsant activity mediated by gamma-aminobutyric acid (GABA) was examined using intracerebral injections of GABA agonists. Blockade of tonic hindlimb extension in the maximal electroshock test and blockade of tonic and clonic seizures produced by pentylenetetrazole and bicuculline were obtained by elevating GABA in the ventral midbrain tegmentum. Elevation of GABA in forebrain and hindbrain areas had no effect on convulsant activity. Blockade of tonic and clonic seizures was also obtained after microinjections of the direct GABA receptor agonist, muscimol, into the midbrain. The substantia nigra was identified as the critical midbrain site for GABA-mediated anticonvulsant activity. Local injection of GABA agonists into the midbrain provided seizure protection without a widespread augmentation of GABA-mediated activity throughout the brain and without impairing either alertness or motor function. Synapses in the substantia nigra appear to represent an important control mechanism for inhibiting the propagation of generalized convulsions.