Lamotrigine positively affects the development of psychiatric comorbidity in epileptic animals, while psychiatric comorbidity aggravates seizures

Several clinical and preclinical studies have focused on the relationship between epilepsy and psychological disturbances. Although behavior in some experimentalmodels of epilepsy has been studied, only few of them can be considered as modelsof epilepsy and mood disorder comorbidity. Since several models of epilepsy orpsychiatric disorders are already available, we wondered whether a mixture of thetwo could experimentally represent a valid alternative to study such comorbidity.Here, we present a possible experimental protocol to study drug effects andphysiopathogenesis of psychiatric comorbidity in epileptic animals.Pentylentetrazol-kindled animals were subjected to the chronic mild stress (CMS) procedure; furthermore, we tested the effects of chronic lamotrigine treatment onthe development of comorbidity. We found that epileptic-depressed animals showed more pronounced behavioral alterations in comparison to other mice groups,indicating that kindled animals develop more pronounced CMS-induced behavioralalterations than nonepileptic mice; lamotrigine was able to prevent thedevelopment of comorbidities such as anxiety, depression-like behavior, andmemory impairment.