ANTICONVULSANT ACTION OF BOTH NMDA AND NON-NMDA RECEPTOR ANTAGONISTS AGAINST SEIZURES INDUCED BY HOMOCYSTEINE IN IMMATURE RATS

Seizures were induced in immature 18-day-old rats by i.p. administrati on of homocysteine (11 mmol/kg) and the effects of selected antagonist s of NMDA receptors [MK-801 (0.5 mg/kg), AP7 (0.33 mmol/kg), CGP 40116 (10 mg/kg)] and non-NMDA receptors [GDEE (4 mmol/kg), NBQX (two doses , 30 mg/kg each)] were studied. The effect of MgSO4 (two doses, 2 mmol /kg each) was also tested. The anticonvulsant effect was evaluated not only from the behavioral manifestations of seizures, but also in term s of some indicators of brain energy metabolism. Rat pups were sacrifi ced during generalized clenic-tonic seizures, corresponding to 16-45 m in after homocysteine administration. Comparable time intervals were u sed for sacrificing the pups which had received the protective drugs. In contrast to neonatal rats, in which only NMDA antagonists could pre vent homocysteine-induced seizures, both NMDA and non-NMDA receptor an tagonists exerted an anticonvulsant effect in 18-day-old rats. In addi tion, the pronounced anticonvulsant effect could be achieved by the co mbined treatment with low subthreshold doses of NMDA (MK-801) and non- NMDA (NBQX) receptor antagonists. The protection was evident not only in suppressing behavioral symptoms of seizures, but also in preventing most of the metabolic changes accompanying seizures, mainly glycogen degradation. More than a sevenfold accumulation of lactate occurring d uring seizures was markedly reduced by all the tested drugs, but was n ot completely eliminated. All antagonists, when given alone in the sam e doses as those used for seizure protection, remained without any eff ect on lactate levels. Comparison of the present data with previous fi ndings concerning neonatal rats suggests that there may be a developme ntal change in anticonvulsant efficacy of non-NMDA receptor antagonist s against homocysteine-induced seizures in rats. (C) 1997 Academic Pre ss.