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An Appetitive Spatial Working Memory Task for Mice in a Semi-Automated 8-Arm Radial Maze, Reducing Fearful Memory Association in the Maze
Published on: July 29, 2025
Facilitating effect of histamine on spatial memory deficits induced by dizocilpine as evaluated by 8-arm radial maze
Yu-Wen Huang1, Zhong Chen, Wei-Wei Hu
1Department of Neurobiology and Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310031, China.
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 microg/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 alpha-fluoromethylhistidine (alpha-FMH, 5 microg/site, ih), a potent and selective histidine decarboxylase (HDC) inhibitor, and H1-antagonist pyrilamine (1 microg/site, ih), but not by H2-antagonist cimetidine, even at a high dose (2.5 microg/site, ih).
Conclusion:
The hippocampal histamine plays an important role in the ameliorating effect on MK-801-induced spatial memory deficits, and its action is mediated through postsynaptic H1-receptor.

