Pharmacology of epileptogenesis and related comorbidities in the WAG/Rij rat model of genetic absence epilepsy.

Animal studies currently represent the best source of information also in the field of epileptogenesis research. Many animal models have been proposed and studied so far both from the pathophysiological and pharmacological point of view. Furthermore, they are widely used for the identification of potentially clinically valuable biomarkers. The WAG/Rij rat model, similarly to other genetic animal strains, represents a suitable animal model of absence epileptogenesis accompanied by depressive-like and cognitive comorbidities. Generally, animal models of epileptogenesis are characterized by an identifiable initial insult (e.g. traumatic brain injury), a latent phase lasting up to the appearance of the first spontaneous seizure and a chronic phase characterized by recurrent spontaneous seizures. In most of genetic models: the initial insult should be defined as the mutation causing epilepsy, which is not clearly defined in the WAG/Rij rat model; the latent phase ends at the appearance of the first spontaneous seizure, which is about 2-3 months of age in WAG/Rij rats and thereafter the chronic phase. WAG/Rij rats also display depressive-like comorbidity around the age of 4 months, which is apparently linked to the development of absence seizures considering both its ontogeny and the fact that drugs affecting absence seizures development also block the development of depressive-like behavior. Finally, WAG/Rij rats also display cognitive impairment in some memory tasks, however, this has not been yet definitively linked to absence seizures development and may represent an epiphenomenon. This review is focused on the effects of pharmacological treatments against epileptogenesis and their effects on comorbidities.