HIGH EXPRESSION OF NORADRENALINE, CHOLINE-ACETYLTRANSFERASE AND GLIALFIBRILLARY ACIDIC PROTEIN IN THE EPILEPTIC FOCUS CONSECUTIVE TO GABA WITHDRAWAL - AN IMMUNOCYTOCHEMICAL STUDY

Interruption of a chronic GABA infusion into the rat somatosensory cor tex induces the appearance of focal epileptic manifestations, known as the 'GABA withdrawal syndrome' (GWS). The aim of the present study wa s to determine, by immunocytochemistry, if neurotransmitters other tha n GABA are involved in GWS, namely: noradrenaline (NA), serotonin, cho line acetyltransferase (CAT), cholecystokinin, neuropeptide Y, somatos tatin and glial fibrillary acid protein (GFAP). Immunocytochemical dat a were compared in three animal groups: GABA-, saline- and L-aspartate (L-Asp)-infused rats. Only GABA-infused rats presented epileptic mani festations after interruption of the infusion. Saline- and L-Asp-infus ed rats served as controls. Observations were limited to the region su rrounding the cortical infusion site. GABA-infused rats showed in the zone of the epileptic focus a number of cell bodies strongly immunorea ctive to NA antibodies much larger than control rats. In addition, NA- immunoreactive fibers formed a dense plexus and some of them were obse rved around perikarya. In saline- and L-Asp-infused rats, the NA-immun olabelled fibers were sparse and NA immunolabelling was rarely observe d in cell bodies. These results contrast to those obtained for the ser otonergic system, where no significant difference was observed among t he three groups of rats. CAT immunolabelling was observed in cell bodi es, but not in nerve terminals in rats of the three groups. The number of CAT-immunoreactive cell bodies was much greater in GABA-infused ra ts than in the control animals. GFAP immunolabelling showed an importa nt number of astrocytes throughout the cortex of the GABA-infused hemi sphere, whereas, astrocytic reaction was limited to the infusion site in controls. Immunocytochemical data concerning peptides revealed cort ical neuronal elements labelled similarly in the three groups of rats. Noradrenergic, cholinergic and glial modifications observed mainly in GABA-infused rats can result from lesion and from a specific action o f GABA in chronic infusion. These modifications may contribute to the epileptogenesis of GWS, as recently demonstrated by electrophysioloica l recordings that show a modulating action of NA on firing activity of neurons involved in the epileptic focus.