Prolonged anticonvulsant action of glutamate metabotropic receptor agonists in inferior colliculus of genetically epilepsy-prone rats

Abstract

The anticonvulsant activity of ( S)-4-carboxy-3-hydroxyphenylglycine (( S)-4C3HPG) (an antagonist of Group I and an agonist of Group II metabotropic glutamate (mGlu) receptors), of (1 S,3 S)-1-aminocyclopentane-1,3-dicarboxylic acid ((1 S,3 S)-ACPD) (an agonist of Group II mGlu receptors), and of l-serine- O-phosphate (an agonist of Group III mGlu receptors) was studied against sound-induced seizures in genetically epilepsy-prone (GEP) rats following bilateral microinjection into the inferior colliculus. All 3 drugs produce dose-dependent suppression of all phases of sound-induced seizures (wild running, clonic and tonic). ( S)-4C3HPG produces an immediate and short-lasting (<2 h) protection against sound-induced seizures with an ED 50 value of 4.3 (3.2–5.7) nmol, at 5 min. The preferential agonists of Group II and Group III mGlu receptors produce an immediate, transient (<10 min) proconvulsant effect followed by a prolonged (>1 day) anticonvulsant effect against sound-induced seizures. The anticonvulsant ED 50 value for (1 S,3 S)-ACPD is 9 (5–18) nmol at 2 h, and for l-serine- O-phosphate is 36 (6.5–199) nmol at 2 days. It is concluded that mGlu receptor activation potently modifies seizure threshold.