INTRAHIPPOCAMPAL ADMINISTRATION OF A GLYCINE SITE ANTAGONIST IMPAIRS WORKING-MEMORY PERFORMANCE OF RATS

The effects of 7-chlorokynurenic acid, an antagonist at the glycine site associated with the NMDA receptor/channel complex, on memory functions were investigated using a three-panel runway task. In a working memory task, 7-chlorokynurenic acid at a dose of 3.2 mu g/side, injected bilaterally into the dorsal hippocampus, significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points). The working memory deficit induced by intrahippocampal 7-chlorokynurenic acid (3.2 mu g/side) was reversed by concurrent injection (32 mu g/side) of D-serine, the glycine site agonist. In a reference memory task, 7-chlorokynurenic acid had no effect on the number of errors when injected into the hippocampus at doses up to 3.2 mu g/side. These results suggest that activation of the hippocampal glycine site coupled to the NMDA receptor is required for working memory function in rats.