Glycine potentiates diazepam anticonvulsant activity in electroshock seizures of rats: Possible sites of interaction in the brainstem

Abstract

The effect of orally or intracerebrally injected glycine on the anticonvulsant actions of intraperitoneal diazepam was examined using a tonic-clonic electroshock seizure model in the rat. Orally administered glycine (1.125 g/kg) potentiated the anticonvulsant effect of diazepam (DZP) to convert tonic-clonic electroshock seizures to less severe subthreshold clonic seizures. Oral glycine by itself had no effect on the tonic-clonic seizure response. Bilateral substantia nigra (SN) microinjections of glycine (125 μg/site) failed to potentiate intraperitoneal DZP when compared with the most appropriate control, animals treated with DZP and intranigral saline. It was not possible to determine whether bilateral glycine microinjections into the inferior olivary nucleus (IO) potentiated anticonvulsant effects of DZP since glycine alone converted all tonic-clonic seizures to the clonic response. Finally, bilateral glycine microinjection alone into the nucleus reticularis pontis oralis (PNO) produced an anticonvulsant effect when compared to untreated control responses but did not potentiate the anticonvulsant actions of DZP. Although these results may indicate that the glycinergic potentiation of DZP involves a direct pharmacodynamic interaction between these two compounds at specific brain sites, these sites have not yet been demonstrated conclusively.