Anticonvulsant action of a kainate antagonist gamma-D-glutamyl aminomethylsulphonic acid injected focally into the substantia nigra and entopeduncular nucleus

Abstract

Focal injection of gamma-D-glutamylaminomethylsulphonic acid (GAMS) into basal ganglia areas, the substantia nigra and entopeduncular nucleus, protects against electroshock (50 mA, 60 Hz, 0.2 s) and pilocarpine (380 mg/kg i.p.) induced seizures in rats. GAMS infusion into substantia nigra pars reticulata significantly protects against generalised (5, 10 nmol) and limbic (10, 50 nmol) seizures. The highest dose of GAMS results in similar suppression of seizure activity following injection into substantia nigra pars compacta against generalised (10 nmol) and limbic (50 nmol) seizures. The anticonvulsant action of GAMS is less marked after infusion into the entopeduncular nucleus. High doses of GAMS are required to provide protection against electroshock test (10 nmol) and limbic (40 nmol) seizures. Protection against limbic and electroshock seizures is more pronounced after infusion of GAMS into substantia nigra than into the entopeduncular nucleus. The substantia nigra pars reticulata is particularly sensitive to the anticonvulsant action of GAMS suggesting that antagonism at the kainate receptor is functionally important.