D-cycloserine, a glycine site agonist, reverses working memory failure by hippocampal muscarinic receptor blockade in rats.
D-Cycloserine, a partial agonist at the glycine binding site on the NMDA receptor/channel complex, did not affect the number of errors (attempts to pass through two incorrect panels of the three-panel gates at four choice points) in the working memory task with a three-panel runway setup, when injected bilaterally at 1 or 10 microg/side into the dorsal hippocampus. Intrahippocampal administration of the muscarinic receptor antagonist scopolamine (3.2 microg/side) significantly increased the number of working memory errors. The increase in working memory errors induced by intrahippocampal 3.2 microg/side scopolamine was significantly reduced by concurrent infusion of 1 and 10 microg/side D-cycloserine. These results suggest that positive modulation of the NMDA receptor/channel through activation of the glycine site can compensate dysfunction of hippocampal cholinergic neurotransmission involved in working memory function.
Ohno
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Watanabe
S
S
D000818:Animals; D003523:Cycloserine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000819:agonists*; D011976:Receptors, Muscarinic / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology; D009435:Synaptic Transmission
D018009:Receptors, Glycine; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine; D012601:Scopolamine