Role of neurotransmitter aminoacids in generation of cortical epileptic after discharges during ontogenesis
Med Sci Monit 1999; 5(3): BR385-391
Background: Epileptic seizures usually originate as an imbalance between neuronal excitation and inhibition. Two principal ways how to reinstate this balance were tested in our model of myoclonic seizures: a suppression of proconvulsant effects of excitatory amino acids or potentiation of anticonvulsant effects of GABAergic inhibition. Additionally, a combination of both approaches was determined.
Material/Methods: NMDA receptor antagonists (CGP 40116, AP7, dizocilpine) as well as GABA-acting drugs (phenobarbital, clobazam, bretazenil, NNC-711, baclofen and CGP 35348) were tested in three age groups of rats (12, 18 and 25 day old) in the model of neocortical electrically-induced EEG and motor seizures. Three parameters were evaluated: 1. intensity of motor seizures accompanying electrical stimulations, 2. duration of EEG discharges, and 3. intensity of motor seizures accompanying EEG discharges.
Results: All NMDA receptor antagonists exhibited the highest anticonvulsant effect in our model of myoclonic seizures in 25 day old animals. The order of anticonvulsant potency against EEG discharges was: CGP 40116 (competitive antagonist) > AP7 (competitive antagonist) > dizocilpine (noncompetitive antagonist). All drugs facilitating GABAA inhibition (phenobarbital, clobazam, bretazenil and NNC-711) had similar anticonvulsant action in all age groups and were more effective in 25 day old animals. Baclofen as a GABAB agonist displayed only small anticonvulsant activity with weakest anticonvulsant effects in 18 day old rats. GABAB antagonist CGP 35348 had proconvulsant effects in EEG discharges but not in motor manifestations in all age groups. The anticonvulsant effects of the combination of sodium valproate and CGP 40116 were not significantly better than the effects of monotherapy with either drug.
Conclusions: In contrast to other developmental seizure models, we found that both the NMDA receptor antagonists and GABA-acting drugs were more effective against myoclonic seizures in prepubertal rats.
Keywords: electrical stimulation, development, Anticonvulsant drugs, Epileptogenesis, Rats, Seizures, sensorimotor region