Age-dependent phenytoin effects on cortical stimulation in rats

The effects of phenytoin on threshold intensities of stimulation were studied in cortical epileptic afterdischarges (ADs) in 12-day-old and adult rats with implanted electrodes. Stimulation of the sensorimotor cortical area induced movements directly related to the stimulation as well as EEG afterdischarges (ADs) of the spike-and-wave type and of the limbic type. Rat pups exhibited lower thresholds for stimulation-bound movements and spike-and-wave ADs than adult animals. On the contrary, the limbic type of ADs was elicited with lower current intensity in adult than in immature rats. Phenytoin increased the threshold for stimulation-related movements only in adult rats, whereas threshold intensities for spike-and-wave ADs were increased and thresholds for limbic type of ADs remained uninfluenced in both age groups. The age-dependent effect on stimulation-related movements might be due to a maturation of connectivity in the motor system or to developmental changes in the voltage-gated sodium channels as the main target of phenytoin action.