[Animal models of epilepsy and experimental seizures]

Animal models of epilepsy are essential for the search of new effective antiepileptic drugs. Moreover they may lead to the discovery of the basic neuronal dysfunction(s) which underlies human epilepsies. Animal epilepsies as well as experimental seizures are usually considered as valid models of human epilepsies when, and only when, the drugs which are effective in human epilepsies prevent seizures in animals. This, however, precludes finding new drugs for resistant epilepsies. Animal models of epilepsy can be classified as follows: (i) experimental seizures induced by convulsant drugs or by an electrical stimulation; (ii) reflex epilepsies; (iii) idiopathic epilepsies. Examples of animal models of epilepsy taken from each of these three classes are briefly reviewed. Seizures induced by convulsant drugs or by an electroshock are widely used as simple and rapid screening systems for new anticonvulsant compounds. Moreover, the use of chemical convulsants can lead to new hypotheses concerning the mechanisms underlying human epilepsies. Thus, one of the main arguments in favor of the GABAergic hypothesis of epilepsy is that GABA antagonists induce seizures which are readily counteracted by most antiepileptic drugs. Among the other models of experimentally induced seizures, the kindling model is usually considered, on the basis of its pharmacological characteristics, as a Grand Mal type epilepsy model. Thirty years after this model was first described, the exact modifications induced in the brain by the kindling procedure remain unknown. Various animal species exhibit reflex epilepsies. Myoclonic seizures can be induced by photic stimulation in Papio-papio baboons; tonic-clonic seizures can be induced by various auditory stimuli in certain strains of mice and rats; myoclonic and tonic-clonic seizures can be induced by a variety of environmental stimuli in the mongolian gerbil; photosensitive and febrile seizures have been described in fowl. Most antiepileptic drugs are effective in these reflex epilepsies. Alterations in several neurotransmitter systems have been reported in susceptible strains as compared to resistant strains, such as modifications in noradrenergic, serotoninergic, GABAergic or glutamatergic transmissions, but no single abnormal parameter can unequivocally be correlated to seizure susceptibility. Idiopathic epilepsy is not uncommon in dogs and the prevalence of the disease appears to be comparable to that observed in man. Grand Mal type epilepsy appears to be the most frequent type of epilepsy in dogs; little work has been devoted to the study of the neurochemical alterations which may underly the disease.