The present study has examined the
anticonvulsant and
neuroprotective effect of (S)-3,4-dicarboxyphenylglycine ((S)-3,4-DCPG), a highly selective agonist for subtype 8 of group III
metabotropic glutamate receptors (mGluRs), against
seizures induced in immature 12-day-old rats by bilateral icv infusion of
DL-homocysteic acid (DL-HCA, 600 nmol/side). For biochemical analyses, rat pups were sacrificed during generalized clonic-
tonic seizures, approximately 45-50 min after infusion. Comparable time intervals were used for sacrificing the animals which had received (S)-3,4-DCPG (0.25 nmol/each side, 15-20 min prior to infusion of DL-HCA or saline). This agonist provided a pronounced
anticonvulsant effect, generalized clonic-
tonic seizures were completely suppressed and cortical energy metabolite changes which normally accompany these
seizures were either normalized (decrease of
glucose and
glycogen) or markedly reduced (an accumulation of
lactate).
Anticonvulsant effect of (S)-3,4-DCPG was also evident from the EEG recordings, nevertheless, it was not complete. In spite of the absence of obvious motor phenomena, sporadic ictal activity could be seen in some animals. Isolated spikes could also be observed in some animals after administration of (S)-3,4-DCPG alone. The
neuroprotective effect of (S)-3,4-DCPG was evaluated after 24 h and 6 days of survival following DL-HCA-induced
seizures. Massive neuronal degeneration was observed in a number of brain regions following infusion of DL-HCA alone (seizure group), whereas pretreatment with (S)-3,4-DCPG provided substantial neuroprotection. The present findings suggest that receptor subtype 8 of group III mGluRs may be considered a promising target for
drug therapy in childhood
epilepsies in the future.