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.
The action of phenytoin was studied in acute experiments in rats with brainstem transection at the midcollicular level. Symmetrical epileptogenic foci were elicited in sensorimotor cortical areas of both hemispheres by local application of penicillin. Seven rats formed a control group, ten animals were pretreated with phenytoin (60 mg/kg i.p., 10 min before penicillin application). Synchronization of interictal discharges in control rats was delayed in comparison to animals with an intact brainstem; phenytoin did not influence this synchronization. Spontaneous transition of interictal into ictal activity was not abolished by phenytoin, i.e. in cerveau isolé preparations phenytoin lost this activity. The loss of anticonvulsant activity was not complete. Ictal episodes were modified; they started as very short ones and their duration progressively increased. Structures localized below the level of transection represent a site of at least one of the mechanisms of phenytoin anticonvulsant action.
Action of carbamazepine (50 mg/kg i.p.) and phenytoin (60 mg/kg i.p.) on the activity of cerebellar neurones was studied in rats under urethane anaesthesia. Carbamazepine markedly decreased the firing frequency of all ten neurones recorded continually before and after drug administration. The same conclusion was reached when a group of 53 cells recorded before drug administration was compared with 48 neurones recorded after carbamazepine administration only. The effects of phenytoin were ambiguous - a decrease as well as an increase in frequency was recorded. The solvent used did not change cerebellar unit activity. Cerebellum cannot be considered as a possible target structure for phenytoin but it might be a target for carbamazepine action.
The action of phenytoin and valproate on thalamocortical responses was studied in adult rats. Single responses were not influenced by either drug. Paired-pulse potentiation of the initial components (first positive and first negative) observed with intervals from 50 to 200 ms under control conditions was abolished by phenytoin (60 mg/kg i.p.) but only moderately influenced by valproate (400 mg/kg i.p.). Paired-pulse potentiation of thalamocortical phenomena cannot be put into connection with the generation of the spike-and-wave rhythm.