Noradrenergic abnormalities in the genetically epilepsy-prone rat

The genetically epilepsy-prone rat (GEPR) has central nervous system noradrenergic deficits as compared to normal rats. It is possible that these deficits contribute to seizure predisposition because they are exhibited 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 noradrenergic activity in brain. Neurochemical studies indicate that deficits exist in areas innervated by both the locus ceruleus and the lateral tegmental noradrenergic systems. These deficits exist in GEPRs without seizure experience and are more pronounced in the severe seizure strain as compared to the moderate seizure strain. We review eight experimental steps undertaken to identify more precisely the anatomical location of noradrenergic determinants of seizure predisposition. These steps illustrate the theoretical bases for the studies and describe the specific experiments completed. Evidence supports the hypothesis that noradrenergic deficits in the superior colliculus and/or ventrally adjacent regions are determinants of seizure predisposition.