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.
Peterson
S L
SL
Department of Medical Pharmacology and Toxicology, Texas A&M University Health Science Center, College Station 77843-1114.
D000818:Animals; D000927:Anticonvulsants; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D003523:Cycloserine / Q000494:pharmacology*; D004597:Electroshock; D007839:Functional Laterality; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*
D000927:Anticonvulsants; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid