EFFECTS OF INTRAVENTRICULAR LOCUS-COERULEUS TRANSPLANTS ON SEIZURE SEVERITY IN GENETICALLY EPILEPSY-PRONE RATS FOLLOWING DEPLETION OF BRAINNOREPINEPHRINE

Audiogenic seizures (AGS) in genetically epilepsy-prone rats (GEPR) of the moderate-seizure substrain (GEPR-3s) were investigated to determi ne whether norepinephrine (NE) depletion induced by 6-hydroxydopamine (6-OHDA) microinfusion into the locus coeruleus (LC) could alter the e fficacy of intraventricular NE tissue grafts in promoting reductions i n seizure severity in AGS. GEPR-3s were stereotaxically infused with 6 -OHDA (4 mu g/side/rat), or vehicle into the region of the LC. Followi ng 6-OHDA treatment all animals were subjected to 3 AGS tests. GEPR-3s seizure severities were increased in 39.5% of the animals after micro infusion of 6-OHDA into the region of the LC. Following the third AGS test, each rat was stereotaxically implanted with 17 gestational day r at fetal tissue obtained from the dorsal pens and containing the primo rdia of the LC or with tissue obtained from the neocortex or were sham -grafted. Subsequent to grafting, rats were subjected to 3 additional AGS tests. 53% (10/19) of 6-OHDA treated GEPRs showed a significant re duction in seizure severity following transplantation of fetal LC tiss ue. In contrast, only 20% (1/5) of GEPRs infused with saline rather th an 6-OHDA showed a reduction of seizure severity following fetal LC tr ansplantation. NE content in the cortex and pons/medulla was decreased by 78% and 46% respectively following 6-OHDA microinfusion into the L C. Prominent grafts with numerous TH positive neurons and neurites wer e present within the third ventricle of grafted animals, while cortex grafts contained no TH immunostained structures. These findings sugges t that the efficacy of fetal LC tissue to promote reductions in seizur e severity in GEPRs is increased following depletion of central NE by microinfusion of 6-OHDA.