Paradoxical anticonvulsant activity of the gamma-aminobutyrate antagonist bicuculline methiodide in the rat striatum

Abstract

Bicuculline methiodide (BMI), a gamma-aminobutyrate (GABA) antagonist, is a powerful convulsant agent when injected into the cerebral ventricles, amygdala, hippocampus, thalamus, neocortex, and deep prepiriform cortex in rats. In contrast, bilateral microinjection of BMI into the rat striatum confers protection against seizures induced by the cholinergic agonist pilocarpine (380 mg/kg, i.p.), with an ED50 of 94 fmol (range 45-195 fmol). No topographical variation in the anticonvulsant action of BMI was detected throughout rostrocaudal and dorsoventral aspects of the striatum. The anticonvulsant action of BMI in the striatum was reversed by coadministration of the GABA agonist muscimol or by blocking GABA-mediated inhibition in either the substantia nigra pars reticulata or in the entopeduncular nucleus. The results show that blockade of GABA-mediated inhibition in the striatum has a powerful anticonvulsant effect in the pilocarpine model, suggesting that GABAergic transmission in the striatum modulates the seizure propagation in the forebrain.