Previous studies demonstrated that selected agonists for metabotropic
glutamate group II and group III receptors can provide protection against
seizures in adult animals. The present study has examined the potential effect of some of these compounds on
seizures induced in immature rats by
intracerebroventricular infusion of
DL-homocysteic acid (DL-HCA, 600 nmol/side). Rat pups were sacrificed during generalised clonic-
tonic seizures, 50--60 min after infusion. Comparable time intervals were used for sacrificing the pups which had received the
protective drugs. The
anticonvulsant effect was evaluated according to the suppression of behavioural manifestations of
seizures and the protection of energy metabolite changes which normally accompany these
seizures (large decreases of
glucose and
glycogen, and approximately 7- to 10-fold accumulation of
lactate). Partial protection was exhibited by group II mGluR agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (
DCG IV, 0.6 nmol) and this effect was abolished after pretreatment with an antagonist for group II mGluRs (RS)-alpha-methyl-4-tetrazolylphenylglycine (MTPG, 100 nmol). In high doses (5--100 nmol), however,
DCG IV evoked
seizures which were prevented by AP7, suggesting that the
convulsant effect was mediated by interaction with
NMDA receptors. A pronounced
anticonvulsant effect against DL-HCA-induced
seizures was achieved with low doses of a highly selective group II mGluR agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC, 0.6 nmol), group II agonist and group I mGluR antagonist (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4-C3HPG, 0.6 nmol) and group III mGluR agonist (RS)-1-amino-3-(phosphonomethylene) cyclobutane-
carboxylic acid (32 nmol). Generalised clonic--
tonic seizures were completely suppressed and the metabolic changes were markedly ameliorated, there being only a 1.5-, 2- and 2.5-fold rise of
lactate, respectively. Higher doses of (S)-4-C3HPG (1--100 nmol) were, however, less
anticonvulsant than low doses. The present results have confirmed that mGluRs may be considered a potential target for treatment of
epilepsy.