Effects of nicardipine, an antagonist of L-type voltage-dependent calcium channels, on kindling development, kindling-induced learning deficits and hippocampal potentiation phenomena

Kindling is considered to be a useful experimental model for investigating drug effects on the convulsive component of epilepsy and related alteration s at the behavioural level. It was demonstrated that pentylenetetrazol (PTZ )-kindled rats show diminished learning performance in shuttle-box training . We used this model to study the influence of nicardipine, an antagonist o f L-type voltage-dependent calcium channels, on kindling seizure developmen t as well as related learning impairments. Additionally, we tested the infl uence of nicardipine on kindling-induced potentiation, a special form of lo ng-term enhancement of evoked potentials in the dentate gyrus after kindlin g. Therefore, monosynaptic evoked field potentials in the dentate area upon test stimuli to the perforant pathway were recorded in freely moving kindl ed and control rats at different times after injection of PTZ. The results indicate that the blockade of L-type voltage-dependent Ca2+-channels during the kindling procedure attenuates PTZ-kindling, antagonizes a kindling-ind uced learning deficit in an active avoidance test and decreases a novel for m of kindling-related potentiation, the long-lasting amplitude enhancement of the monosynaptic evoked held potential in the dentate gyrus after inject ion of a small test dose of PTZ. This potentiation can also be prevented in kindled animals by nicardipine injection in an acute experiment. (C) 1999 Elsevier Science Ltd. All rights reserved.