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 micrograms/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 micrograms/side) was reversed by concurrent injection (32 micrograms/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 micrograms/side. These results suggest that activation of the hippocampal glycine site coupled to the NMDA receptor is required for working memory function in rats.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
M
M
Ohno
T
T
Yamamoto
S
S
Watanabe
D000818:Animals; D001665:Binding Sites; D005998:Glycine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D016194:Receptors, N-Methyl-D-Aspartate; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; D005998:Glycine