NORADRENERGIC ABNORMALITIES IN THE GENETICALLY EPILEPSY-PRONE RAT

The genetically epilepsy-prone rat (GEPR) has central nervous system n oradrenergic deficits as compared to normal rats. It is possible that these deficits contribute to seizure predisposition because they are e xhibited by seizure-naive as well as by seizure-experienced GEPRs. On the basis of pharmacological studies, it is hypothesized that there is an inverse relation between seizure predisposition and levels of nora drenergic activity in brain. Neurochemical studies indicate that defic its exist in areas innervated by both the locus ceruleus and the later al tegmental noradrenergic systems. These deficits exist in GEPRs with out seizure experience and are more pronounced in the severe seizure s train as compared to the moderate seizure strain. We review eight expe rimental steps undertaken to identify more precisely the anatomical lo cation of noradrenergic determinants of seizure predisposition. These steps illustrate the theoretical bases for the studies and describe th e specific experiments completed. Evidence supports the hypothesis tha t noradrenergic deficits in the superior colliculus and/or ventrally a djacent regions are determinants of seizure predisposition.