Effects of the NMDA antagonist MK-801 on radial maze performance in histidine-deficient rats.
We examined the effects of a histidine-deficient diet on brain histamine contents as well as on learning and memory using the eight-arm radial maze in rats. A significant decrease in histamine content in the hippocampus was observed after long-term feeding of rats with a histidine-deficient diet. At the same time, significant enhancement of the acquisition process in radial maze performance was also observed. Pyrilamine did not show a significant effect on radial maze performance in histidine-deficient rats. On the other hand, pyrilamine caused a significant spatial memory deficit in control rats. Scopolamine was effective in inhibiting spatial memory in both histidine-deficient and control rats. MK-801 caused spatial memory deficits more potently in histidine-deficient rats than in controls. Brain glycine contents showed a significant increase in the hippocampus in histidine-deficient rats. These results indicated that the spatial memory deficits induced by MK-801 in histidine-deficient rats are closely related to increased glycine levels and activation of NMDA receptors.
Nishiga
Miyuki
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Sugimoto
Yukio
Y
Taga
Chiyomi
C
Fujii
Yoko
Y
Kamei
Chiaki
C
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004032:Diet; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006639:Histidine / Q000172:deficiency; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology
D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; D006634:Histamine H1 Antagonists; D006639:Histidine; D016291:Dizocilpine Maleate; D012601:Scopolamine; D011738:Pyrilamine