Active avoidance learning in WAG/Rij rats with genetic predisposition to absence epilepsy

Neurological disorders are often accompanied by impairment of memory, attention deficit that cause learning difficulties. Better understanding of learning problems in neurological patients might help to improve the quality of their life. Here we studied the character of fear-based associative learning using the standard active avoidance test in WAG/Rij rats with genetic predisposition to absence epilepsy. Electroencephalographic properties of spike-wave seizures (i.e., hallmarks of absence epilepsy) were examined at the age of 5 and 7 m. Around 24 % of rats did not express epileptic activity despite genetic predisposition. In the active avoidance test, 6 m old rats with the epileptic phenotype needed more trails to obtain the first avoidance than non-epileptic rats, but showed the same number of avoidances to reach the learning criterion. The total time of spike-wave activity positively correlated with the outcomes of avoidance performance only in subjects with severe epilepsy, but not in subjects with mild epilepsy. In order to evaluate early sensory (epigenetic) factors governing cognitive comorbidities in adult WAG/Rij rats, we performed bilateral whisker trimming during PN1-8 and PN9-16. This led to a quicker development of SWD, but did not influence cognitive abilities at the age of 6 m. In summary, epileptic WAG/Rij rats had difficulties with executive functions before the first avoidance of adverse stimulus, rather than impairment of memory after the first avoidance. Our data assume that cognitive comorbidities in epileptic WAG/Rij rats primarily may relate to executive deficit during the initial stage of avoidance test and secondary to impairment of short-term memory. This fits well to outcomes of clinical studies in patients with generalized epilepsy.