AIM: To investigate whether or not histamine is involved in spatial memory deficits induced by dizocilpine (MK-801) as evaluated by 8-arm radial maze of rats. METHODS: 8-Arm (4-arm baited) radial maze was used to measure spatial memory in rats. RESULTS: Bilaterally intrahippocampal (ih) injection of MK-801 (0.3 μg/site) impaired working memory and reference memory in rats. Both histamine (50, 100 ng/site, ih) and intraperitoneal (ip) injection of histidine (100, 200 mg/kg) markedly improved the spatial memory deficits induced by MK-801. On the other hand, the ameliorating effect of histidine (100 mg/kg, ip) was completely antagonized by α-fluoromethylhistidine (α-FMH, 5 μg/site, ih), a potent and selective histidine decarboxylase (HDC) inhibitor, and H_1-antagonist pyrilamine (1 μg/site, ih), but not by H_2-antagonist cimetidine, even at a high dose (2.5 μg/site, ih). CONCLUSION: The hippocampal histamine plays an important role in the ameliorating effect on MK-801-induced spatial memory deficits, AIM: To investigate whether or not histamine is involved in spatial memory deficits induced by dizocilpine (MK-801) as evaluated by 8-arm radial maze of rats. METHODS: 8-Arm (4-arm baited) radial maze was used to measure Spatial memory in rats. RESULTS: Bilaterally intrahippocampal (ih) injection of MK-801 at 0.3 μg / site impaired working memory and reference memory in rats. Both histamine (50, 100 ng / site, On the other hand, the ameliorating effect of histidine (100 mg / kg, ip) was completely antagonized by α-fluoromethylhistidine (α- FMH, 5 μg / site, ih), a potent and selective histidine decarboxylase (HDC) inhibitor, and H 1 -targeting pyrilamine (1 μg / site, ih), but not by H_2-antagonist cimetidine, even at a high dose μg / site, ih). CONCLUSION: The hippocampal histamine plays an important role in the ameliorating effect on MK-801-induced spatia l memory deficits,