Localization of an anatomic substrate for the anticonvulsant activity induced by D-cycloserine

D-Cycloserine is a partial agonist of the strychnine-insensitive glycine site that inhibits the tonic hindlimb extension (THE) component of maximal electroshock seizures (MES). This study determined the effect of focal D-clycoserine microinfusion into nucleus reticularis pontis oralis (RPO) on the THE component of MES in rats. Bilateral microinfusion of D-cycloserine (50 nmol per side) into the RPO region 5.4 and 5.6 mm posterior to bregma inhibited THE in 80% of rats tested. Unilateral D-cycloserine (50 nmol) RPO microinfusions were ineffective. Likewise, RPO microinfusion of vehicle, L-cycloserine (50 nmol per side), or the strychnine-insensitive glycine site antagonist 7-chlorokynurenic acid (10 and 50 nmol per side) did not alter THE incidence. However, coinfusion of 7-chlorokynurenic acid (50 nmol per side) with D-cycloserine (50 nmol per side) completely antagonized the anticonvulsant activity induced by D-cycloserine (8 of 8 rats with THE). These data indicate that the anticonvulsant activity of D-cycloserine is mediated by RPO. Because the anticonvulsant effect is stereospecific and is reversible by 7-chlorokynurenic acid, these results also indicate that D-cycloserine acts through the strychnine-insensitive glycine site to inhibit THE.