Effect of age on pentylenetetrazol-kindling and kindling-induced impairments of learning performance

Epileptogenesis during ontogeny may not be linearly related to time. It is known that the behavioral manifestations of seizures are age-dependent, but more research is needed to clarify ontogenetic aspects of epilepsies and related alterations, including cognitive deficits. Kindling is an accepted animal model for the study of the convulsive component of epilepsy and its consequences on behavior. Recently, we demonstrated an impairment in acquisition of a conditioned reaction in young adult kindled rats, using pentylenetetrazol (PTZ) as the kindling stimulus. The present study was undertaken to investigate the dependence on age of alterations in the induction of PTZ kindling in rats. We started the kindling protocol in 4-, 6-, and 8-week- and 6-, 12-, 18-, and 24-month-old rats. The PTZ kindling showed an age-dependent decrease in expression of convulsions. The diminished kindling capacity was already seen in 6-month-old rats. In contrast, kindling-related impairment effects on cognitive functions increased with age. Thus, the correlation between learning impairment and occurrence of tonic-clonic seizures that we had demonstrated in 8-week-old rats was abolished in older rats. On the other hand, when the kindling procedure was started in 6-week-old rats, no impairment was found in fully kindled rats.