Role of noradrenergic ascending system in extinction of epileptic phenomena

This chapter reviews results which show that in electroshock-induced and chemically induced convulsions, audiogenic seizures of genetic epilepsy-prone rats and mice, in the kindling focus and the cobalt lesion seizure, susceptibility is modulated by a noradrenergic mechanism. In general, mechanisms that increase or decrease norepinephrine activities decrease or increase seizures, respectively, in these models. In the kindling phenomenon, since the seizure itself provokes an increase in norepinephrine (NE) turnover, with decreased beta-adrenoceptor binding and hyposensitivity to ionophoretic catecholamine application, down regulation could be the cause of hyperexcitability or a consequence of it. In the cobalt focus, supersensitivity to NE appeared when NE-containing terminal density decreased (denervation supersensitivity) and beta-receptor sites increased greater than 50%. Perfusion experiments with NE support the hypothesis that the cortical NE system inhibits the spread of chronic epileptogenic activities in the cobalt focus. In the quaking mouse and in the tottering mouse, noradrenergic dysfunction underlying epileptogenesis may be expressed as a hyperinnervation.