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 anticonvulsant action of 1,5-benzodiazepine clobazam was studied in 12-, 18-, and 25-day-old rats. Cortical epileptic afterdischarges (ADs) elicited by rhythmic electrical stimulation of the sensorimotor cortical area were used as a model in animals with implanted electrodes. As far as the duration of ADs is concerned, clobazam in doses of 1 or 5 mg/kg i.p. blocked the progressive increase with repeated stimulations in all age groups and the higher dose significantly shortened ADs in 25-day-old rats. The intensity of movements accompanying stimulation was decreased only by the 5 mg/kg dose in 25-day-old animals, whereas clonic seizures were less intense after both doses in 12- and 25-day-old rat pups. Clobazam exerted an anticonvulsant action at all the developmental stages studied; the lower efficacy in 18-day-old rats (described also for clonazepam) remains to be analyzed.
Threshold intensities for elicitation of movements and of epileptic afterdischarges by rhythmic stimulation of the sensorimotor cortex were estimated in 90 rats with implanted electrodes. Four age groups were studied - animals 12, 18, 25 and 90 days old. Both thresholds exhibited significantly higher values for adult animals in comparison with all groups of young pups. Whereas no differences were found among the rat pups in thresholds for movements accompanying stimulation, epileptic afterdischarges demonstrated a lower threshold in 18-day- old in comparison with 25-day-old animals. The development of cortical excitability is rather complicated and deserves further studies.
Activation of GABAB receptors leads to longer inhibitory postsynaptic potentials than activation of GABAA receptors. Therefore GABAB receptors may be a target for anticonvulsant therapy. The present study examined possible effects of GABAB receptor agonist SKF97541 on cortical and hippocampal epileptic afterdischarges (ADs). Epileptic ADs elicited by electrical stimulation of sensorimotor cortex or dorsal hippocampus were studied in adult male Wistar rats. Stimulation series were applied 6 times with 10- or 20-min interval. Either interval was efficient for reliable elicitation of cortical ADs but stimulation at 10-min intervals did not reliably elicit hippocampal ADs, many stimulations were without effect. SKF97541 in dose 1 mg/kg significantly prolonged cortical ADs. Duration of hippocampal ADs was not significantly changed by either dose of SKF97541 in spite of a marked myorelaxant effect of the higher dose. Our present data demonstrated that neither cortical nor hippocampal ADs in adult rats were suppressed by GABAB receptor agonist SKF97541. Proconvulsant effect on cortical ADs indicates a different role in these two brain structures. In addition, duration of refractory period for electrically-induced ADs in these two structures in adult rats is different., P. Fábera, P. Mares., and Obsahuje bibliografii
Epileptic afterdischarges elicited by electrical stimulation of the dorsal hippocampus in freely moving rats were not significantly changed by flunarizine administration in comparison with control sessions in which the animals received the solvent only. On the other hand, flunarizine significantly reduced the number of wet dog shakes, the main automatisms accompanying limbic afterdischarges.
The possible protective action of pramiracetam, a pyrrolidinone nootropic drug, against hypobaric hypoxia was studied in two age groups of immature rats with implanted electrodes. Epileptic afterdischarges induced by hippocampal stimulation were used as a measure of hypoxic damage. Pramiracetam did not substantially change these afterdischarges in 12- and 18-day-old rat pups which were not exposed to hypoxia. Hypobaric hypoxia (simulated altitude of 7000 m for one hour) led to prolongation of the first afterdischarge in both age groups. Pramiracetam did not influence this prolongation in 12-day-old rats. The first afterdischarge was shortened significantly in 18-day-old animals but not to the level of rats not exposed to hypoxia. The afterdischarges elicited by repeated stimulations (four times at 10 min intervals) did not differ in pramiracetam-treatcd and control rats.