Effects of glycine receptor antagonism on spreading depression in the rat

Spreading depression (SD) in the rat brain is inhibited by N-methyl-D-aspartate (NMDA) receptor antagonists. Because the NMDA receptor glycine recognition site must be occupied for activation of the NMDA ionophore, we hypothesized that antagonism of the glycine receptor would also affect SD. In halothane anesthetized rats, SD was initiated by electrocortical stimulation. Both the initiation threshold and propagation rate of SD were recorded. Rats were then administered the glycine receptor antagonist ACEA-1021 (or vehicle only) or ketamine and the stimulus was repeated. Rats were then killed and terminal depolarization was observed for. Ketamine completely inhibited initiation of SD. In contrast, all rats treated with ACEA-1021 exhibited SD. While ACEA-1021 caused no difference in the stimulation threshold for SD, propagation rate was decreased in a dose-dependent fashion. Terminal depolarization occurred in all rats. Antagonism of glycine at the NMDA receptor recognition site did not inhibit initiation of SD but played a modulatory role in the mechanism of its propagation.