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 alterations 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 of L-type voltage-dependent calcium channels, on kindling seizure development as well as related learning impairments. Additionally, we tested the influence of nicardipine on kindling-induced potentiation, a special form of long-term enhancement of evoked potentials in the dentate gyrus after kindling. Therefore, monosynaptic evoked field potentials in the dentate area upon test stimuli to the perforant pathway were recorded in freely moving kindled 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-induced learning deficit in an active avoidance test and decreases a novel form of kindling-related potentiation, the long-lasting amplitude enhancement of the monosynaptic evoked field potential in the dentate gyrus after injection of a small test dose of PTZ. This potentiation can also be prevented in kindled animals by nicardipine injection in an acute experiment.
Hassan
H
H
Institute of Pharmacology and Toxicology, Medical Faculty of Otto-von-Guericke University Magdeburg, Germany. hadir.hassan@medizin.uni-magdeburg.de
Grecksch
G
G
Rüthrich
H
H
Krug
M
M
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D003292:Convulsants; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D003292:Convulsants; D009529:Nicardipine; D010433:Pentylenetetrazole