SEIZURE DEVELOPMENT AND NORADRENALINE RELEASE IN KINDLING EPILEPSY AFTER NORADRENERGIC REINNERVATION OF THE SUBCORTICALLY DEAFFERENTED HIPPOCAMPUS BY SUPERIOR CERVICAL-GANGLION OR FETAL LOCUS-COERULEUS GRAFTS

Solid pieces of fetal locus coeruleus (LC) or superior cervical gangli on (SCG) were placed into a fimbria-fornix lesion cavity in 6 hydroxyd opamine-treated, noradrenaline (NA)-denervated rats. Six to 8 months l ater, all animals were subjected to electrical kindling stimulations i n the hippocampus until they had reached the fully kindled state. Nong rafted lesioned animals showed markedly increased kindling rate which was partly attenuated by LC but not SCG grafts. In both LC- and SCG-gr afted animals, dopamine beta-hydroxylase immunocytochemistry demonstra ted a high density of graft-derived noradrenergic fibers in the dorsal hippocampus, whereas reinnervation of the ventral hippocampus was muc h more sparse. Subregional distribution of these fibers within the hip pocampus was different in the two grafted groups. Both grafts partly r estored basal extracellular NA levels in the hippocampus and reacted t o generalized seizures by a significant (two- to threefold) increase o f NA release, as measured by intracerebral microdialysis. Our data ind icate (i) that seizure activity can regulate transmitter release from noradrenergic neurons in both LC and SCG grafts, (ii) that only fetal LC grafts retard seizure development in kindling, and (iii) that the i nability of SCG implants to influence kindling epileptogenesis could b e due to a lack of synaptic contacts between the graft-derived ganglio nic fibers and host hippocampal neurons. (C) 1994 Academic Press, Inc.