Neurotransmitter abnormalities as determinants of seizure susceptibility and intensity in the genetic models of epilepsy.

Normal subjects are not considered to be epileptic merely because they exhibit a seizure in response to an appropriate stimulus of sufficient intensity. In epileptics, a relatively weak stimulus will elicit an explosive neuronal response, whereas in a normal individual it will cause only trivial responses. Fortunately, only a few subjects in any given animal or human population are epileptic; however, most if not all epileptics are genetically predisposed to seizures. The importance of genetic determinants in human epilepsy has become established only recently [l]. Genetic factors probably control seizure susceptibility and, therefore, the likelihood of developing epilepsy [l-8]. The genetic determinant is not solely responsible for the appearance of seizures but is an important contributing component. Seizures probably do not occur in the absence of other factors such as stress, biochemical and hormonal imbalances, or other environmental or physical initiators [l]. Thus, epilepsy is a composite of the individual’s genetically controlled seizure propensity plus the presence of one or more seizure triggering factors. We believe that neurochemical studies in subjects with a genetically determined predisposition to seizures are helping establish the molecular basis of epileptogenicity. However, heretofore most investigations of epilepsy have used animal models with very high degrees of inherited seizure resistance. These are normal animals which are made “epileptic” by the use of various chemical or electrical methods. Except in the kindling model of epilepsy, these normal animals retain their relatively high innate seizure resistance. Although valuable information has been obtained on the initiation of seizures in normal animals, this approach has revealed very little about genetically determined seizure susceptibility. Genetic models of epilepsy. At least one genetic model of epilepsy is available within each of several animal species, including the rat [9, 101, mouse