SEIZURE SUPPRESSION IN KINDLING EPILEPSY BY INTRACEREBRAL IMPLANTS OFGABA-RELEASING BUT NOT BY NORADRENALINE-RELEASING POLYMER MATRICES

Gamma-aminobutyric acid (GABA)-releasing polymer matrices were implant ed bilaterally, immediately dorsal to the substantia nigra, in rats pr eviously kindled in the amygdala. Two days after implantation, rats wi th GABA-releasing matrices exhibited only focal limbic seizures in res ponse to electrical stimulation, whereas animals with control matrices devoid of GABA had generalized convulsions. GABA release from the pol ymer matrices was high during the first days after implantation, as de monstrated both in vitro and, using microdialysis, in vivo. The antico nvulsant effect was no longer observed at 7 and 14 days at which time GABA release was found to be low. In a parallel experiment, polymer ma trices containing noradrenaline (NA) were implanted bilaterally into t he hippocampus of rats with extensive forebrain NA depletion induced b y an intraventricular 6-hydroxydopamine injection. No effect on the de velopment of hippocampal kindling was observed, despite extracellular NA levels exceeding those of rats with intrahippocampal locus coeruleu s grafts that have previously been shown to retard kindling rate. The results indicate that GABA-releasing implants located in the substanti a nigra region can suppress seizure generalization in epilepsy, even i n the absence of synapse formation and integration with the host brain . In contrast, the failure of NA-releasing polymer matrices to retard the development of seizures in NA-depleted rats suggests that such an effect can only be exerted by grafts acting through a well-regulated, synaptic release of NA.