7-Chlorokynurenic acid antagonizes the anticonvulsant activity of d-cycloserine in maximal electroshock seizures

Abstract

This study evaluated the anticonvulsant activity of d-cycloserine against maximal electroshock seizures in rats. Systemically administered d-cycloserine (i.p.) inhibited maximal electroshock-induced tonic hindlimb extension in a dose-dependent manner with an ED 50 of 153 mg/kg. No neurological deficit was detected at any dose of d-cycloserine. In contrast, l-cycloserine had no effect on the maximal electroshock seizures. Administration of the strychnine-insensitive glycine receptor antagonist 7-chlorokynurenic acid (100 nmol i.c.v.) significantly antagonized the anticonvulsant activity induced by d-cycloserine. Centrally administered d-cycloserine (i.c.v.) induced significant anticonvulsant activity 1–2 h after administration with an approximate ED 50 of 5 μmol. 7-Chlorokynurenic acid (100 nmol i.c.v.) significantly antagonized the anticonvulsant activity of centrally administered d-cycloserine. l-Cycloserine (i.c.v., 2 h) induced no significant anticonvulsant activity. These results provide evidence that the anticonvulsant activity of d-cycloserine in maximal electroshock seizures may be mediated by strychnine-insensitive glycine receptors.